Information

What are the characteristics of a cancerous cell surface membrane?

What are the characteristics of a cancerous cell surface membrane?



We are searching data for your request:

Forums and discussions:
Manuals and reference books:
Data from registers:
Wait the end of the search in all databases.
Upon completion, a link will appear to access the found materials.

A notable characteristic of cancer is that it thrives at a high glycolytic rate, and doesn't require much aerobic respiration. I am curious, how does the cell surface membrane composition change so that less oxygen is able to diffuse into cancerous cells? Does the membrane become more rigid? Or how do the fatty acid tails, cholesterol, etc change?


Micro- and Nanoengineering of the Cell Surface

Micro- and Nanoengineering of the Cell Surface explores the direct engineering of cell surfaces, enabling materials scientists and chemists to manipulate or augment cell functions and phenotypes. The book is accessible for readers across industry, academia, and in clinical settings in multiple disciplines, including materials science, engineering, chemistry, biology, and medicine. Written by leaders in the field, it covers numerous cell surface engineering methods along with their current and potential applications in cell therapy, tissue engineering, biosensing, and diagnosis.

The interface of chemistry, materials science, and biology presents many opportunities for developing innovative tools to diagnose and treat various diseases. However, cell surface engineering using chemistry and materials science approaches is a new and diverse field. This book provides a full coverage of the subject, introducing the fundamentals of cell membrane biology before exploring the key application areas.

Micro- and Nanoengineering of the Cell Surface explores the direct engineering of cell surfaces, enabling materials scientists and chemists to manipulate or augment cell functions and phenotypes. The book is accessible for readers across industry, academia, and in clinical settings in multiple disciplines, including materials science, engineering, chemistry, biology, and medicine. Written by leaders in the field, it covers numerous cell surface engineering methods along with their current and potential applications in cell therapy, tissue engineering, biosensing, and diagnosis.

The interface of chemistry, materials science, and biology presents many opportunities for developing innovative tools to diagnose and treat various diseases. However, cell surface engineering using chemistry and materials science approaches is a new and diverse field. This book provides a full coverage of the subject, introducing the fundamentals of cell membrane biology before exploring the key application areas.


Cell Membrane Structure

Encyclopaedia Britannica / UIG / Getty Images

The cell membrane is primarily composed of a mix of proteins and lipids. Depending on the membrane’s location and role in the body, lipids can make up anywhere from 20 to 80 percent of the membrane, with the remainder being proteins. While lipids help to give membranes their flexibility, proteins monitor and maintain the cell's chemical climate and assist in the transfer of molecules across the membrane.


Characteristics of Cancer Cells

For the most part, normal cells adopt a specific, uniform cell shape once they differentiate. Depending on the cell, this may allow the cell to effectively perform their function in the body.

A good example of this is red blood cells that have a biconcave shape that allows them to carry red blood cells effectively. Cancer cells, on the other hand, are irregular in shape and misshapen with varying sizes.

Given that they do not attach to each other as other normal cells do (in various tissues) they also appear as a chaotic collection of cells when viewed under the microscope.

The irregular shape of cancer cells has also been identified in the nucleus and nucleolus of cancer cells. Whereas normal cells have a nucleus with a smooth appearance that is spherical in shape, the nucleus of cancer cells tends to be irregular with bulges (blebs). This irregularity is also evident on the nucleolus and may be divided into multiple nucleoli.


Unit 5 - final

All cells must be self-sufficient along with holding an ability to reproduce this can be in forms of binary fusion, mitosis or meiosis. The life span of every cell is variable. All cells require an energy source, many are from metabolic pathways and stored in the form of adenosine triphosphate. Cells will require this energy to respire which may be anaerobic or aerobic (depending upon the use of oxygen). As well as making use of enzymes and catalysts for a faster chemical reaction. Normally, cells grow to a certain size and then stop. Cells cease growing because of intrinsic and extrinsic factors. Growth factors are proteins in the cell’s environment that attach to the plasma membrane, directing cells to continue growing. Growth factors cause cells to grow without initiating cell division.

Prokaryotic and Eukaryotic Cells

Prokaryotic Cells

Prokaryotic cells member bound organelles (nucleus and

Mitochondria). Bacteria are amongst the simplest of

organisms - they are made of single cells. Their cell structure is simpler than the cells of eukaryotes and cells are smaller, most are 0.2 μm - 2.0 μm. Prokaryotic are one of the simplest cells of life, they reproduce very quickly and achieve cell division using binary fission meaning the cell will spilt into two identical cells. Prokaryotic cells are anaerobic (respire without the use of oxygen), this happens within the cytoplasm, their DNA is a single circular chromosome called plasmids and is contained in the central are by the nucleoid. (Bitesize 2020)

Eukaryotic Cells

Eukaryotic cells are cells that contain a nucleus and organelles, and are enclosed by a plasma membrane. Organisms that have eukaryotic cells include protozoa, fungi, plants and animals. Eukaryotic cells

are larger and more complex than prokaryotic cells, which are found in Archaea and Bacteria, the other two domains of life.

Comparison

Prokaryotic and Eukaryotic cells are the division of two living organisms. All cells fall into one of these categories, whilst they do share a lot of similarities, they have a unique structure and function differently. For example both sets of cells are made up of DNA as a genetic material but a defining feature is that eukaryotic cells have a nucleus classing this as complex cell were as a prokaryotic cell has no nucleus which classes this as a simple cell. Eukaryotic cells are found within animals and plants were as prokaryotic cells are found within bacteria. I have created a table below show the key differences between the two cells:

No Organelles Cytoskeleton

Simple cell structure Complex cell structure

No Membrane organelles Membrane organelles

Primitive Contains a cell wall

DNA is free within nucleus DNA within nucleus

Smaller cells 10x larger prokaryotic cells

Can respire without the use of oxygen Depends on oxygen on whether it can respire

Lysosomes and Peroxisomes absent Lysosomes and Peroxisomes present

Cytoskeleton absent Cytoskeleton present

I have created a table Eukaryote sub-cellar structure and organelles:

Organelle Structure Function Nucleus  Largest membrane (organelle)  Double nuclear membrane and nuclear pore

The nucleus is the largest membrane-bound organelle, it has a double nuclear membrane and a nuclear pore. Described as the hub of a cell.

Cytoplasm  Contains salts, sugars, enzymes and amino acids  Located within the cell membrane Often referred to as a cytosol. The cytoplasm contains enzymes, sugars, salts, amino acids, and nucleotides. The enzymes are used for metabolic reactions, Located within the cell membrane.

 Long shape  Double membrane

Most important function is to produce energy, stores it as ATP molecules. It also referred as the ‘powerhouse cell’.

Ribosomes  Smallest membrane (organelle)  Most common found  Found in the cytoplasm  Attach themselves to the rough endoplasmic reticulum Ribosomes are the smallest organelle, they are the most numerous found. They are the site where proteins are made and synthesized. They are found within the cytoplasm, also attach themselves to the surface of the rough endoplasmic reticulum (RER)

Cytoskeleton  Made from microfilaments and microtubules  Contains shape and motility (due to above bullet point)

The cytoskeleton is made up of microfilaments and microtubules, the main purpose of this is to maintain the cells' shape, support, and motility.

Nucleolus  Made from chromatin  Part of the creation of ribosomes  Located within nucleus

This is made up of chromatin and is involved in the manufacturing of ribosomes. Located within the nucleus.

 Contains digestive enzymes to break down old cells, food molecules, old organelles and pathogens

Breaks down and removes wastes, digests dead, damaged cells which pose threats - bacteria.

 Flattened membranes  Also referred to as ‘cisternae’  Proteins move through Golgi body  Receives proteins from RER

The Golgi body is a series of flattened membranes referred to as cisternae. Its primary function is to receive proteins from the RER and repackage these for use or secretion. Proteins are moved throughout the Golgi body being modified if necessary. As transferred the membrane pinches inward to form vesicles.

Gained Nutrients and Waste Products

The cell membrane excerpts waste and gains nutrients by from transferring substances, this can be in all different ways depending upon the substances nature. A few ways a membrane does this is explained below:

Lipid

Lipid diffusion is used for steroid transportation. The Lipid bilayer allows small substances such as oxygen, carbon dioxide, and hydrophobic molecules to pass through the cell membrane and then pass down their concentration gradient into simple diffusion.

Facilitated

Facilitated diffusion is also used through concentration gradient with non-recurring energy and then classed as a passive transport. Facilitated diffusion is also known for the diffusion of solutes through transporting proteins in the plasma membrane classed as channels and carriers.

Passive Transport

Passive transport occurs when molecules diffuse across the cell membrane by passing through certain transportation proteins. The transportation happens when a high concentration molecules needs to go to a lower concentration. There is no use of energy in this as it goes with the concentration gradient. BBC Bitesize 2020

Active Transport

Active transport occurs when molecules at a low concentration are moved by different transport proteins across the cell membrane into a higher concentration. This movement require energy as it goes against the concentration gradient. ‘Energy is provided by the breakdown of ATP inside the cell. (BBC Bitesize 2020)’.

Vesicular transport

Vesicular transport is the predominant exchange of proteins and lipids between membrane- bound organelles in eukaryotic cells. There are three types of transport vesicles, as shown below:

  1. Clathrin Coated – Clathrin coated vesicles are formed from both the plasma membrane and the trans- Golgi network.
  2. COPI Coated COPI coated vesicles and COPII-coated emerge from the endoplasmic reticulum (ER) in order to export new proteins towards the Golgi.
  3. COPI - COPI vesicles appear in both biosynthetic (anterograde) and retrograde transport, within the Golgi complex. COPI mainly recycles proteins from the Golgi to the endoplasmic reticulum (ER).

Golgi-derived COPI-coated vesicles are involved in several vesicular transport steps, including bidirectional transport within the Golgi and recycling to the ER. (Company of Biologists 2020)

Respiration

ATP is made within the respiration process ATP can be hydrolyzed into ADP/PI with the use of active transport. ATP is vital to cell’s survival as it will release energy when require for chemical reactions. It is dependent on the trophic levels of food to provide energy sources to be chemically changed into ATO. The mode widely used substrate for respiration is glucose, but may use proteins and liquids. Energy nutrients can be stored for future use. The three stages to cellular respiration are

  1. Glycolysis – This occurs within the cytoplasm and can happen with or without oxygen.
  2. Krebs cycle – it is a complex series of biochemical pathways which is better known as above, this occurs within the mitochondria and is a series of chemical reactions to release stored energy (BD editors 2019)
  3. Electron transport – this is the final stage of respiration, this occurs within the inner membrane of the mitochondria

molecules for this process are proteins, lipids, carbohydrates, nucleic acids such as DNA and RNA. The anabolism process takes smaller molecules and builds them up into more complex ones, using the energy fuelled through ATP. The smaller molecules are joined to make bigger and different molecules referred to as macromolecules. Anabolism use these macromolecules to build cells and help new cells which are essential for growth, building organs and tissues. (BBC Bitesize, 2020)

Here are the few functions of Animal Cell:

  1. These cells control the processes in the body efficiently.
  2. Cells control synthesis and storage of energy.
  3. Cells also perform and control the Replication, Translation, and transcription of DNA.
  4. Cells are extremely dedicated to carrying out precise responsibilities.
  5. Red blood cells encompassed of Hemoglobin. Hemoglobin is the cells which did not contain any nuclei and its main function is to transfer oxygen throughout the whole body.
  6. Inside the human body, ciliary cells are present in the Digestive Tract which increase the surface area and help in the process digestion.
  7. Numerous cells syndicate and form Tissues. Which perform a specialised function in the human body.
  8. Analogous tissues assembled and form the organs of the body, like lungs, brain and heart.

Nucleus Acids

Nucleic acids are essential biomolecules that are present in every form of life that we live in. They are present in all organisms from animals and bacteria to viruses and humans. Nucleic acids range in size from small biomolecules to large biopolymers. They are made up of repetitive subunits called nucleotides. The word nucleic acid is used for DNA and RNA.

Both nucleic differ in size, shape, location and function within the cell, as shown below.

RNA is also present in almost all living cells. RNA is the second most important nucleic acid present in the living things. It is a polymer of ribonucleotides having ribose as pentose sugar.

Transfer RNA (tRNA)

Transfer RNA transfers amino acids to the ribosomes so that they can be assembled into proteins. The RNA reads the code on the messenger (mRNA) RNA and carries the specific amino acids to the ribosomes so it can be transferred to the correct proteins.

Messenger RNA (mRNA)

The messenger RNA is responsible for the messages between the DNA and cytoplasm. It carries information for the present proteins within the nucleus of DNA to the ribosomes in the cell cytoplasm.

Ribosomal RNA (rRNA)

Ribosomal RNA is the most abundant RNA present in cells. It is an essential component of ribosomes present in bacterial and eukaryotic cells. The ribosomal RNA arranges itself into two subunits, a larger ribosomal subunit and a smaller ribosomal subunit. The structure of these two subunits differs in prokaryotes and eukaryotes.

Cell Division and Daughter Cells

Within cell division there are two different types of cells mitosis and meiosis. Cell division is the reproductive mechanism where all living organisms develop and produce off spring.

Actively dividing eukaryote cells pass through a series of stages known collectively as the cell cycle: two gap phases (G1 and G2) an S (for synthesis) phase, in which the genetic material is duplicated and an M phase, in which mitosis partitions the genetic material and the cell divides.

Mitosis - When the mitosis cell cycle is complete, the cell divides into two daughter cells. Mitosis cells develop two identical body cells for growth and repair (when body becomes damaged it creates more cells). All cells must create genetic information in order to be identical to the parent cell.

Prophase - During early prophase chromosomes become visible as coiled threads which condense to shorten and thicken. As prophase progresses the centrioles move to opposite poles of the nucleus. The nuclear membrane envelopes down to disappear.

Metaphase - During metaphase the spindle becomes fully formatted, chromosomes become lined up at the equator of this spindle and pairs of chromatids attach to it by their centromere.

Anaphase - Here the chromatids are pulled apart by the movement of the spindle fibres splitting to become newly separated chromatids which are then referred to as chromosomes. Sister chromatids will move in the opposite direction towards the pole.

Telophase - Telophase is the final stage of mitosis, as the reach the poles of the spindle, chromatids uncoil and become invisible. The nuclear membrane reforms around each group, as the nucleolus reforms in each nucleus. Spindle fibres disintegrate. Each new cell will contain a copy of the DNA that it begins to replicate as the cell re-enters interphase.

There are two main steps of the cell cycle, interphase where the growth of the cell takes place, it is also the longest phase, where the dividing cell spends 90-95% of its time in preparation for mitosis phase.

G1 phase - Metabolic changes prepare the cell for division. At a certain point - the restriction point - the cell is committed to division and moves into the S phase.  S phase - DNA synthesis replicates the genetic material. Each chromosome now consists of two sister chromatids.  G2 phase - Metabolic changes assemble the cytoplasmic materials necessary for mitosis and cytokinesis.  M phase - A nuclear division (mitosis) followed by a cell division (cytokinesis).

The period between mitotic divisions - that is, G1, S and G2 - is known as interphase.

Interphase is broken down into 3 sub-phases. Gap 1 (G1) new cells go through normal growth and synthesise high amounts of protein, preparing to replicate DNA. Some organelles are produced, the cell grow and increases in volume. Only once the cell has synthesised enough ribosomes can it move into next phase. Synthesis (S) is the period in which DNA is replicated and the number of chromosomes also doubled. Gap 2 (G2) is the final stage, the cell continues to increase in size and replenish energy stores.

This is the cell cycle as shown starting with cell growth, then DNA synthesis after that further growth occurs and the DNA is checked for errors. The cell can only divide once it’s made copies of the organelles, then after dividing it has a resting period.

Meiosis –Meiosis is used in sexual reproduction, which then creates gametes. These are seen within animals, pollen and ova in plants as their sperm and egg. One diploid cell produces four haploid gametes, in two divisions.

This is the cell process that happens in the reproductive organs of both males and females. The chromosones create idential copies of themseleves then similar chromosones will pair up. After the sections of the DNA will get swapped then the division will happen and the second divison and soforeth.

Cancer

Cells

All Cancer cells begin as a normal cell and it then becomes damaged versions of normal cells, normally this is down to adnormalities rather than single mutation. Cancer is caused by changes to a person’s DNA through chemicals or other agents called carcinogens. The carcinogens damage the DNA causing mutations, this causes the cell cycle to go wrong and stops correct signals being sent to cells, as cancer is a non-communicable disease. Cells may then divide when not needed, the mitosis stage then becomes uncontrolled. It is at this point that cancer cells may develop cells take control of their own growth and divide many times unchecked a lump of cells can form which is known as a tumour, were as (shown in the above image) normal cells stay very controlled and don’t grow at an abnormal rate and create clusters. I have created a table below that shows the difference between a cancer cell and a normal cell:

Organelles and Charteristics

I think cell biology is one of the most important subjected needed to learn within the science sector because it makes us understand how we live.

Recommendations

As stated in previous units using the pomodoro techinque has allowed me to finish this unit a lot faster than I normally would as I was giving myself breaks inbetween studying so I would not become fatigued.

I have used mainly BBC Bitesize for this unit and a few other websites from general research. I have also watched numerous videos on youtube and through BBC Bitesize about cells.


Abstract

Many critical biological processes take place at hydrophobic:hydrophilic interfaces, and a wide range of organisms produce surface-active proteins and peptides that reduce surface and interfacial tension and mediate growth and development at these boundaries. Microorganisms produce both small lipid–associated peptides and amphipathic proteins that allow growth across water:air boundaries, attachment to surfaces, predation, and improved bioavailability of hydrophobic substrates. Higher-order organisms produce surface-active proteins with a wide variety of functions, including the provision of protective foam environments for vulnerable reproductive stages, evaporative cooling, and gas exchange across airway membranes. In general, the biological functions supported by these diverse polypeptides require them to have an amphipathic nature, and this is achieved by a diverse range of molecular structures, with some proteins undergoing significant conformational change or intermolecular association to generate the structures that are surface active.


Membrane

Our editors will review what you’ve submitted and determine whether to revise the article.

Membrane, in biology, the thin layer that forms the outer boundary of a living cell or of an internal cell compartment. The outer boundary is the plasma membrane, and the compartments enclosed by internal membranes are called organelles. Biological membranes have three primary functions: (1) they keep toxic substances out of the cell (2) they contain receptors and channels that allow specific molecules, such as ions, nutrients, wastes, and metabolic products, that mediate cellular and extracellular activities to pass between organelles and between the cell and the outside environment and (3) they separate vital but incompatible metabolic processes conducted within organelles.

Membranes consist largely of a lipid bilayer, which is a double layer of phospholipid, cholesterol, and glycolipid molecules that contains chains of fatty acids and determines whether a membrane is formed into long flat sheets or round vesicles. Lipids give cell membranes a fluid character, with a consistency approaching that of a light oil. The fatty-acid chains allow many small, fat-soluble molecules, such as oxygen, to permeate the membrane, but they repel large, water-soluble molecules, such as sugar, and electrically charged ions, such as calcium.

Embedded in the lipid bilayer are large proteins, many of which transport ions and water-soluble molecules across the membrane. Some proteins in the plasma membrane form open pores, called membrane channels, which allow the free diffusion of ions into and out of the cell. Others bind to specific molecules on one side of a membrane and transport the molecules to the other side. Sometimes one protein simultaneously transports two types of molecules in opposite directions. Most plasma membranes are about 50 percent protein by weight, while the membranes of some metabolically active organelles are 75 percent protein. Attached to proteins on the outside of the plasma membrane are long carbohydrate molecules.

Many cellular functions, including the uptake and conversion of nutrients, synthesis of new molecules, production of energy, and regulation of metabolic sequences, take place in the membranous organelles. The nucleus, containing the genetic material of the cell, is surrounded by a double membrane with large pores that permit the exchange of materials between the nucleus and cytoplasm. The outer nuclear membrane is an extension of the membrane of the endoplasmic reticulum, which synthesizes the lipids for all cell membranes. Proteins are synthesized by ribosomes that are either attached to the endoplasmic reticulum or suspended freely in the cell contents. The mitochondria, the oxidizing and energy-storing units of the cell, have an outer membrane readily permeable to many substances, and a less-permeable inner membrane studded with transport proteins and energy-producing enzymes.


Cell Structure

The cells of protists are among the most elaborate of all cells. Multicellular plants, animals, and fungi are embedded among the protists in eukaryotic phylogeny. In most plants and animals and some fungi, complexity arises out of multicellularity, tissue specialization, and subsequent interaction because of these features. Although a rudimentary form of multicellularity exists among some of the organisms labelled as “protists,” those that have remained unicellular show how complexity can evolve in the absence of true multicellularity, with the differentiation of cellular morphology and function. A few protists live as colonies that behave in some ways as a group of free-living cells and in other ways as a multicellular organism. Some protists are composed of enormous, multinucleate, single cells that look like amorphous blobs of slime, or in other cases, like ferns. In some species of protists, the nuclei are different sizes and have distinct roles in protist cell function.

Single protist cells range in size from less than a micrometer to three meters in length to hectares! Protist cells may be enveloped by animal-like cell membranes or plant-like cell walls. Others are encased in glassy silica-based shells or wound with pellicles of interlocking protein strips. The pellicle functions like a flexible coat of armor, preventing the protist from being torn or pierced without compromising its range of motion.


Affiliations

The Institute for Translational Nanomedicine, Shanghai East Hospital, The Institute for Biomedical Engineering & Nano Science, School of Medicine, Tongji University, Shanghai, 200092, China

Wenjun Le, Bingdi Chen, Zheng Cui, Zhongmin Liu & Donglu Shi

Department of Pathology, School of Medicine, Wake Forest University, Winston-Salem, NC, USA

Department of Mechanical and Materials Engineering, College of Engineering and Applied Science, University of Cincinnati, Cincinnati, OH, USA


References

David-Pfeuty, T. & Singer, S. J. Altered distributions of the cytoskeletal proteins vinculin and α-actinin in cultured fibroblasts transformed by Rous sarcoma virus. Proc. Natl Acad. Sci. USA 77, 6687–6691 (1980).

Tarone, G., Cirillo, D., Giancotti, F. G., Comoglio, P. M. & Marchisio, P. C. Rous sarcoma virus-transformed fibroblasts adhere primarily at discrete protrusions of the ventral membrane called podosomes. Exp. Cell Res. 159, 141–157 (1985).

Chen, W. T., Chen, J. M., Parsons, S. J. & Parsons, J. T. Local degradation of fibronectin at sites of expression of the transforming gene product pp60 src . Nature 316, 156–158 (1985).

Chen, W. T. Proteolytic activity of specialized surface protrusions formed at rosette contact sites of transformed cells. J. Exp. Zool. 251, 167–185 (1989).

Zambonin-Zallone, A., Teti, A., Carano, A. & Marchisio, P. C. The distribution of podosomes in osteoclasts cultured on bone laminae: effect of retinol. J. Bone Miner. Res. 3, 517–523 (1988).

Gimona, M., Buccione, R., Courtneidge, S. A. & Linder, S. Assembly and biological role of podosomes and invadopodia. Curr. Opin. Cell Biol. 20, 235–241 (2008).

Linder, S. & Kopp, P. Podosomes at a glance. J. Cell Sci. 118, 2079–2082 (2005).

Buccione, R., Caldieri, G. & Ayala, I. Invadopodia: specialized tumor cell structures for the focal degradation of the extracellular matrix. Cancer Metastasis Rev. 28, 137–149 (2009).

Stylli, S. S., Kaye, A. H. & Lock, P. Invadopodia: at the cutting edge of tumour invasion. J. Clin. Neurosci. 15, 725–737 (2008).

Clark, E. S. & Weaver, A. M. A new role for cortactin in invadopodia: regulation of protease secretion. Eur. J. Cell Biol. 87, 581–590 (2008).

Weaver, A. M. Invadopodia. Curr. Biol. 18, R362–R364 (2008).

Artym, V. V., Matsumoto, K., Mueller, S. C. & Yamada, K. M. Dynamic membrane remodeling at invadopodia differentiates invadopodia from podosomes. Eur. J. Cell Biol. 90, 172–180 (2011).

Gawden-Bone, C. et al. Dendritic cell podosomes are protrusive and invade the extracellular matrix using metalloproteinase MMP-14. J. Cell Sci. 123, 1427–1437 (2010). This is the first description of highly protrusive podosomes that have the ability to extensively degrade the ECM in a similar manner to invadopodia.

Block, M. R. et al. Podosome-type adhesions and focal adhesions, so alike yet so different. Eur. J. Cell Biol. 87, 491–506 (2008).

Artym, V. V., Zhang, Y., Seillier-Moiseiwitsch, F., Yamada, K. M. & Mueller, S. C. Dynamic interactions of cortactin and membrane type 1 matrix metalloproteinase at invadopodia: defining the stages of invadopodia formation and function. Cancer Res. 66, 3034–3043 (2006).

Clark, E. S., Whigham, A. S., Yarbrough, W. G. & Weaver, A. M. Cortactin is an essential regulator of matrix metalloproteinase secretion and extracellular matrix degradation in invadopodia. Cancer Res. 67, 4227–4235 (2007). This is the first demonstration of the regulated secretion of MMPs at invadopodia.

Linder, S. The matrix corroded: podosomes and invadopodia in extracellular matrix degradation. Trends Cell Biol. 17, 107–117 (2007).

Ayala, I., Baldassarre, M., Caldieri, G. & Buccione, R. Invadopodia: a guided tour. Eur. J. Cell Biol. 85, 159–164 (2006).

Burgstaller, G. & Gimona, M. Podosome-mediated matrix resorption and cell motility in vascular smooth muscle cells. Am. J. Physiol. Heart Circ. Physiol. 288, H3001–H3005 (2005).

Quintavalle, M., Elia, L., Condorelli, G. & Courtneidge, S. A. MicroRNA control of podosome formation in vascular smooth muscle cells in vivo and in vitro. J. Cell Biol. 189, 13–22 (2010). This is the first demonstration that miRNAs can control podosome formation, and the first time that podosomes have been visualized in vivo.

Rottiers, P. et al. TGFβ-induced endothelial podosomes mediate basement membrane collagen degradation in arterial vessels. J. Cell Sci. 122, 4311–4318 (2009). The first visualization of podosomes in ex vivo cultures of endothelial cells.

Varon, C. et al. Transforming growth factor β induces rosettes of podosomes in primary aortic endothelial cells. Mol. Cell Biol. 26, 3582–3594 (2006).

Petrie, R. J., Doyle, A. D. & Yamada, K. M. Random versus directionally persistent cell migration. Nature Rev. Mol. Cell Biol. 10, 538–549 (2009).

Wolf, K. et al. Multi-step pericellular proteolysis controls the transition from individual to collective cancer cell invasion. Nature Cell Biol. 9, 893–904 (2007).

Albiges-Rizo, C., Destaing, O., Fourcade, B., Planus, E. & Block, M. R. Actin machinery and mechanosensitivity in invadopodia, podosomes and focal adhesions. J. Cell Sci. 122, 3037–3049 (2009).

Collin, O. et al. Self-organized podosomes are dynamic mechanosensors. Curr. Biol. 18, 1288–1294 (2008).

Baldassarre, M. et al. Actin dynamics at sites of extracellular matrix degradation. Eur. J. Cell Biol. 85, 1217–1231 (2006).

Abram, C. L. et al. The adaptor protein fish associates with members of the ADAMs family and localizes to podosomes of Src-transformed cells. J. Biol. Chem. 278, 16844–16851 (2003).

Diaz, B. et al. Tks5-dependent, Nox-mediated generation of reactive oxygen species is necessary for invadopodia formation. Sci. Signal. 2, ra53 (2009). This paper provides the first demonstration that ROS control the formation of invadopodia and podosomes.

Oikawa, T., Itoh, T. & Takenawa, T. Sequential signals toward podosome formation in NIH-src cells. J. Cell Biol. 182, 157–169 (2008). This paper describes how invadopodia form near focal adhesions at membrane sites containing PtdIns(3,4)P 2.

Stylli, S. S. et al. Nck adaptor proteins link Tks5 to invadopodia actin regulation and ECM degradation. J. Cell Sci. 122, 2727–2740 (2009).

Seals, D. F. et al. The adaptor protein Tks5/Fish is required for podosome formation and function, and for the protease-driven invasion of cancer cells. Cancer Cell 7, 155–165 (2005). This paper shows that TKS5 is essential for invadopodium formation and invasion, and that its expression can promote invadopodium formation in non-invasive cancer cells.

Destaing, O. et al. β1A integrin is a master regulator of invadosome organization and function. Mol. Biol. Cell 21, 4108–4119 (2010). A mechanistic analysis of how integrins regulate invadopodium and podosome formation.

Tatin, F., Varon, C., Genot, E. & Moreau, V. A signalling cascade involving PKC, Src and Cdc42 regulates podosome assembly in cultured endothelial cells in response to phorbol ester. J. Cell Sci. 119, 769–781 (2006).

Billottet, C. et al. Regulatory signals for endothelial podosome formation. Eur. J. Cell Biol. 87, 543–554 (2008).

Cougoule, C. et al. Three-dimensional migration of macrophages requires Hck for podosome organization and extracellular matrix proteolysis. Blood 115, 1444–1452 (2010).

Ory, S., Brazier, H., Pawlak, G. & Blangy, A. Rho GTPases in osteoclasts: orchestrators of podosome arrangement. Eur. J. Cell Biol. 87, 469–477 (2008).

Berdeaux, R. L., Diaz, B., Kim, L. & Martin, G. S. Active Rho is localized to podosomes induced by oncogenic Src and is required for their assembly and function. J. Cell Biol. 166, 317–323 (2004).

Destaing, O., Saltel, F., Geminard, J. C., Jurdic, P. & Bard, F. Podosomes display actin turnover and dynamic self-organization in osteoclasts expressing actin-green fluorescent protein. Mol. Biol. Cell 14, 407–416 (2003).

Luxenburg, C. et al. The architecture of the adhesive apparatus of cultured osteoclasts: from podosome formation to sealing zone assembly. PLoS ONE 2, e179 (2007).

Alexander, N. R. et al. Extracellular matrix rigidity promotes invadopodia activity. Curr. Biol. 18, 1295–1299 (2008).

Schoumacher, M., Goldman, R. D., Louvard, D. & Vignjevic, D. M. Actin, microtubules, and vimentin intermediate filaments cooperate for elongation of invadopodia. J. Cell Biol. 189, 541–556 (2010). A fascinating microscopic analysis of the temporal elements controlling invadopodium formation and movement through the basement membrane.

Furmaniak-Kazmierczak, E., Crawley, S. W., Carter, R. L., Maurice, D. H. & Cote, G. P. Formation of extracellular matrix-digesting invadopodia by primary aortic smooth muscle cells. Circ. Res. 100, 1328–1336 (2007).

Van Goethem, E. et al. Macrophage podosomes go 3D. Eur. J. Cell Biol. 90, 224–236 (2011).

Van Goethem, E., Poincloux, R., Gauffre, F., Maridonneau-Parini, I. & Le Cabec, V. Matrix architecture dictates three-dimensional migration modes of human macrophages: differential involvement of proteases and podosome-like structures. J. Immunol. 184, 1049–1061 (2010).

Carman, C. V. et al. Transcellular diapedesis is initiated by invasive podosomes. Immunity 26, 784–797 (2007).

Li, A. et al. The actin-bundling protein fascin stabilizes actin in invadopodia and potentiates protrusive invasion. Curr. Biol. 20, 339–345 (2010).

Tolde, O., Rosel, D., Vesely, P., Folk, P. & Brabek, J. The structure of invadopodia in a complex 3D environment. Eur. J. Cell Biol. 89, 674–680 (2010).

Hotary, K., Allen, E., Punturieri, A., Yana, I. & Weiss, S. J. Regulation of cell invasion and morphogenesis in a three-dimensional type I collagen matrix by membrane-type matrix metalloproteinases 1, 2, and 3. J. Cell Biol. 149, 1309–1323 (2000). The first demonstration that MT1MMP is required for 3D but not 2D growth of cancer cells.

Linder, S., Nelson, D., Weiss, M. & Aepfelbacher, M. Wiskott–Aldrich syndrome protein regulates podosomes in primary human macrophages. Proc. Natl Acad. Sci. USA 96, 9648–9653 (1999). The first report implicating a podosome-associated protein in a human disease.

Soriano, P., Montgomery, C., Geske, R. & Bradley, A. Targeted disruption of the c-src proto-oncogene leads to osteopetrosis in mice. Cell 64, 693–702 (1991).

Blouw, B., Seals, D. F., Pass, I., Diaz, B. & Courtneidge, S. A. A role for the podosome/invadopodia scaffold protein Tks5 in tumor growth in vivo. Eur. J. Cell Biol. 87, 555–567 (2008).

Clark, E. S. et al. Aggressiveness of HNSCC tumors depends on expression levels of cortactin, a gene in the 11q13 amplicon. Oncogene 28, 431–444 (2009).

Weaver, A. M. Cortactin in tumor invasiveness. Cancer Lett. 265, 157–166 (2008).

Yamaguchi, H. et al. Molecular mechanisms of invadopodium formation: the role of the N-WASP–Arp2/3 complex pathway and cofilin. J. Cell Biol. 168, 441–452 (2005).

Gatesman, A., Walker, V. G., Baisden, J. M., Weed, S. A. & Flynn, D. C. Protein kinase Cα activates c-Src and induces podosome formation via AFAP-110. Mol. Cell Biol. 24, 7578–7597 (2004).

Yamaguchi, H. & Condeelis, J. Regulation of the actin cytoskeleton in cancer cell migration and invasion. Biochim. Biophys. Acta 1773, 642–652 (2007).

Zambonin-Zallone, A. et al. Immunocytochemical distribution of extracellular matrix receptors in human osteoclasts: a β 3 integrin is colocalized with vinculin and talin in the podosomes of osteoclastoma giant cells. Exp. Cell Res. 182, 645–652 (1989).

Helfrich, M. H. et al. β1 integrins and osteoclast function: involvement in collagen recognition and bone resorption. Bone 19, 317–328 (1996).

Mueller, S. C. & Chen, W. T. Cellular invasion into matrix beads: localization of β1 integrins and fibronectin to the invadopodia. J. Cell Sci. 99, 213–225 (1991).

Nakahara, H. et al. Activation of β1 integrin signaling stimulates tyrosine phosphorylation of p190RhoGAP and membrane-protrusive activities at invadopodia. J. Biol. Chem. 273, 199–212 (1998).

Nakamura, I. et al. Role of αvβ3 integrin in osteoclast migration and formation of the sealing zone. J. Cell Sci. 112, 3985–3993 (1999).

Thomas, S. M. & Brugge, J. S. Cellular functions regulated by Src family kinases. Annu. Rev. Cell Dev. Biol. 13, 513–609 (1997).

Lock, P., Abram, C. L., Gibson, T. & Courtneidge, S. A. A new method for isolating tyrosine kinase substrates used to identify Fish, an SH3 and PX domain-containing protein, and Src substrate. EMBO J. 17, 4346–4357 (1998).

Destaing, O. et al. The tyrosine kinase activity of c-Src regulates actin dynamics and organization of podosomes in osteoclasts. Mol. Biol. Cell 19, 394–404 (2008).

Bromann, P. A., Korkaya, H. & Courtneidge, S. A. The interplay between Src family kinases and receptor tyrosine kinases. Oncogene 23, 7957–7968 (2004).

Obergfell, A. et al. Coordinate interactions of Csk, Src, and Syk kinases with αIIbβ3 initiate integrin signaling to the cytoskeleton. J. Cell Biol. 157, 265–275 (2002).

Dorfleutner, A. et al. Phosphorylation of AFAP-110 affects podosome lifespan in A7r5 cells. J. Cell Sci. 121, 2394–2405 (2008).

Brown, D. I. & Griendling, K. K. Nox proteins in signal transduction. Free Radic. Biol. Med. 47, 1239–1253 (2009).

Grek, C. L. & Tew, K. D. Redox metabolism and malignancy. Curr. Opin. Pharmacol. 10, 362–368 (2010).

Gianni, D. et al. Novel p47phox-related organizers regulate localized NADPH oxidase 1 (Nox1) activity. Sci. Signal. 2, ra54 (2009).

Giannoni, E., Buricchi, F., Raugei, G., Ramponi, G. & Chiarugi, P. Intracellular reactive oxygen species activate Src tyrosine kinase during cell adhesion and anchorage-dependent cell growth. Mol. Cell. Biol. 25, 6391–6403 (2005).

Wu, W. S. et al. Reactive oxygen species mediated sustained activation of protein kinase Cα and extracellular signal-regulated kinase for migration of human hepatoma cell Hepg2. Mol. Cancer Res. 4, 747–758 (2006).

Meng, T. C., Fukada, T. & Tonks, N. K. Reversible oxidation and inactivation of protein tyrosine phosphatases in vivo. Mol. Cell 9, 387–399 (2002).

Baranwal, S. & Alahari, S. K. miRNA control of tumor cell invasion and metastasis. Int. J. Cancer 126, 1283–1290 (2010).

Inui, M., Martello, G. & Piccolo, S. MicroRNA control of signal transduction. Nature Rev. Mol. Cell Biol. 11, 252–263 (2010).

Cordes, K. R. et al. miR-145 and miR-143 regulate smooth muscle cell fate and plasticity. Nature 460, 705–710 (2009).

Elia, L. et al. The knockout of miR-143 and -145 alters smooth muscle cell maintenance and vascular homeostasis in mice: correlates with human disease. Cell Death Differ. 16, 1590–1598 (2009).

Xin, M. et al. MicroRNAs miR-143 and miR-145 modulate cytoskeletal dynamics and responsiveness of smooth muscle cells to injury. Genes Dev. 23, 2166–2178 (2009).

Lu, J. et al. MicroRNA expression profiles classify human cancers. Nature 435, 834–838 (2005).

Chan, K. T., Cortesio, C. L. & Huttenlocher, A. FAK alters invadopodia and focal adhesion composition and dynamics to regulate breast cancer invasion. J. Cell Biol. 185, 357–370 (2009).

Liu, S., Yamashita, H., Weidow, B., Weaver, A. M. & Quaranta, V. Laminin-332–β1 integrin interactions negatively regulate invadopodia. J. Cell Physiol. 223, 134–142 (2010).

Vitale, S., Avizienyte, E., Brunton, V. G. & Frame, M. C. Focal adhesion kinase is not required for Src-induced formation of invadopodia in KM12C colon cancer cells and can interfere with their assembly. Eur. J. Cell Biol. 87, 569–579 (2008).

Hauck, C. R., Hsia, D. A., Ilic, D. & Schlaepfer, D. D. v-Src SH3-enhanced interaction with focal adhesion kinase at β1 integrin-containing invadopodia promotes cell invasion. J. Biol. Chem. 277, 12487–12490 (2002).

Bruzzaniti, A. et al. Dynamin reduces Pyk2 Y402 phosphorylation and Src binding in osteoclasts. Mol. Cell Biol. 29, 3644–3656 (2009).

Duong, L. T. et al. PYK2 in osteoclasts is an adhesion kinase, localized in the sealing zone, activated by ligation of αvβ3 integrin, and phosphorylated by Src kinase. J. Clin. Invest. 102, 881–892 (1998).

Gil-Henn, H. et al. Defective microtubule-dependent podosome organization in osteoclasts leads to increased bone density in Pyk2 −/− mice. J. Cell Biol. 178, 1053–1064 (2007).

Lakkakorpi, P. T., Bett, A. J., Lipfert, L., Rodan, G. A. & Duong le, T. PYK2 autophosphorylation, but not kinase activity, is necessary for adhesion-induced association with c-Src, osteoclast spreading, and bone resorption. J. Biol. Chem. 278, 11502–11512 (2003).

Oser, M. et al. Cortactin regulates cofilin and N-WASp activities to control the stages of invadopodium assembly and maturation. J. Cell Biol. 186, 571–587 (2009). This paper provides a mechanism by which cortactin phosphorylation promotes invadopodium assembly.

Buschman, M. D. et al. The novel adaptor protein Tks4 (SH3PXD2B) is required for functional podosome formation. Mol. Biol. Cell 20, 1302–1311 (2009).

Poincloux, R., Lizarraga, F. & Chavrier, P. Matrix invasion by tumour cells: a focus on MT1-MMP trafficking to invadopodia. J. Cell Sci. 122, 3015–3024 (2009). A comprehensive review of the regulation of MT1MMP trafficking.

Wu, X., Gan, B., Yoo, Y. & Guan, J. L. FAK-mediated Src phosphorylation of endophilin A2 inhibits endocytosis of MT1-MMP and promotes ECM degradation. Dev. Cell 9, 185–196 (2005).

Galvez, B. G., Matias-Roman, S., Yanez-Mo, M., Sanchez-Madrid, F. & Arroyo, A. G. ECM regulates MT1-MMP localization with β1 or αvβ3 integrins at distinct cell compartments modulating its internalization and activity on human endothelial cells. J. Cell Biol. 159, 509–521 (2002).

Bravo-Cordero, J. J. et al. MT1-MMP proinvasive activity is regulated by a novel Rab8-dependent exocytic pathway. EMBO J. 26, 1499–1510 (2007).

Noritake, J., Watanabe, T., Sato, K., Wang, S. & Kaibuchi, K. IQGAP1: a key regulator of adhesion and migration. J. Cell Sci. 118, 2085–2092 (2005).

Sakurai-Yageta, M. et al. The interaction of IQGAP1 with the exocyst complex is required for tumor cell invasion downstream of Cdc42 and RhoA. J. Cell Biol. 181, 985–998 (2008).

Waterman-Storer, C. M., Worthylake, R. A., Liu, B. P., Burridge, K. & Salmon, E. D. Microtubule growth activates Rac1 to promote lamellipodial protrusion in fibroblasts. Nature Cell Biol. 1, 45–50 (1999).

Linder, S., Hufner, K., Wintergerst, U. & Aepfelbacher, M. Microtubule-dependent formation of podosomal adhesion structures in primary human macrophages. J. Cell Sci. 113, 4165–4176 (2000).

Wiesner, C., Faix, J., Himmel, M., Bentzien, F. & Linder, S. KIF5B and KIF3A/KIF3B kinesins drive MT1-MMP surface exposure, CD44 shedding, and extracellular matrix degradation in primary macrophages. Blood 116, 1559–1569 (2010).

Goode, B. L., Drubin, D. G. & Barnes, G. Functional cooperation between the microtubule and actin cytoskeletons. Curr. Opin. Cell Biol. 12, 63–71 (2000).

Badowski, C. et al. Paxillin phosphorylation controls invadopodia/podosomes spatiotemporal organization. Mol. Biol. Cell 19, 633–645 (2008).

Granot-Attas, S., Luxenburg, C., Finkelshtein, E. & Elson, A. Protein tyrosine phosphatase-ɛ regulates integrin-mediated podosome stability in osteoclasts by activating Src. Mol. Biol. Cell 20, 4324–4334 (2009).

Cortesio, C. L. et al. Calpain 2 and PTP1B function in a novel pathway with Src to regulate invadopodia dynamics and breast cancer cell invasion. J. Cell Biol. 180, 957–971 (2008).

Chuang, Y. Y. et al. Role of synaptojanin 2 in glioma cell migration and invasion. Cancer Res. 64, 8271–8275 (2004).

Mukhopadhyay, U. K. et al. Doubles game: Src–Stat3 versus p53–PTEN in cellular migration and invasion. Mol. Cell Biol. 30, 4980–4995 (2010).

Calle, Y., Carragher, N. O., Thrasher, A. J. & Jones, G. E. Inhibition of calpain stabilises podosomes and impairs dendritic cell motility. J. Cell Sci. 119, 2375–2385 (2006).

Blanco, M. J. et al. Correlation of Snail expression with histological grade and lymph node status in breast carcinomas. Oncogene 21, 3241–3246 (2002).

Come, C. et al. Snail and slugs play distinct roles during breast carcinoma progression. Clin. Cancer Res. 12, 5395–5402 (2006).

Yang, J. et al. Twist, a master regulator of morphogenesis, plays an essential role in tumor metastasis. Cell 117, 927–939 (2004).

Kalluri, R. & Weinberg, R. A. The basics of epithelial–mesenchymal transition. J. Clin. Invest. 119, 1420–1428 (2009).

Eckert, M. A. et al. Twist1-induced invadopodia formation promotes tumor metastasis. Cancer Cell 19, 372–386 (2011).

Iqbal, Z. et al. Disruption of the podosome adaptor protein TKS4 (SH3PXD2B) causes the skeletal dysplasia, eye, and cardiac abnormalities of Frank–ter Haar Syndrome. Am. J. Hum. Genet. 86, 254–261 (2010).

Baas, D., Malbouyres, M., Haftek-Terreau, Z., Le Guellec, D. & Ruggiero, F. Craniofacial cartilage morphogenesis requires zebrafish col11a1 activity. Matrix Biol. 28, 490–502 (2009).

Coyle, R. C., Latimer, A. & Jessen, J. R. Membrane-type 1 matrix metalloproteinase regulates cell migration during zebrafish gastrulation: evidence for an interaction with non-canonical Wnt signaling. Exp. Cell Res. 314, 2150–2162 (2008).

Jopling, C. & den Hertog, J. Fyn/Yes and non-canonical Wnt signalling converge on RhoA in vertebrate gastrulation cell movements. EMBO Rep. 6, 426–431 (2005).

McCusker, C., Cousin, H., Neuner, R. & Alfandari, D. Extracellular cleavage of cadherin-11 by ADAM metalloproteases is essential for Xenopus cranial neural crest cell migration. Mol. Biol. Cell 20, 78–89 (2009).

Neuner, R., Cousin, H., McCusker, C., Coyne, M. & Alfandari, D. Xenopus ADAM19 is involved in neural, neural crest and muscle development. Mech. Dev. 126, 240–255 (2009).

Sharma, D., Holets, L., Zhang, X. & Kinsey, W. H. Role of Fyn kinase in signaling associated with epiboly during zebrafish development. Dev. Biol. 285, 462–476 (2005).

Takatsuka, A. et al. Ablation of Csk in neural crest lineages causes corneal anomaly by deregulating collagen fibril organization and cell motility. Dev. Biol. 315, 474–488 (2008).

Cejudo-Martin, P. & Courtneidge, S. A. Podosomal proteins as causes of human syndromes: a role in craniofacial development? Genesis 49, 209–221 (2011).

Kirchhausen, T. Wiskott–Aldrich syndrome: a gene, a multifunctional protein and the beginnings of an explanation. Mol. Med. Today 4, 300–304 (1998).

Monypenny, J. et al. Role of WASP in cell polarity and podosome dynamics of myeloid cells. Eur. J. Cell Biol. 90, 198–204 (2010).

Bonauer, A., Boon, R. A. & Dimmeler, S. Vascular microRNAs. Curr. Drug Targets 11, 943–949 (2010).

Busco, G. et al. NHE1 promotes invadopodial ECM proteolysis through acidification of the peri-invadopodial space. FASEB J. 24, 3903–3915 (2010).

Onodera, Y. et al. Expression of AMAP1, an ArfGAP, provides novel targets to inhibit breast cancer invasive activities. EMBO J. 24, 963–973 (2005).

Kessenbrock, K., Plaks, V. & Werb, Z. Matrix metalloproteinases: regulators of the tumor microenvironment. Cell 141, 52–67 (2010).

Hotary, K. B. et al. Membrane type I matrix metalloproteinase usurps tumor growth control imposed by the three-dimensional extracellular matrix. Cell 114, 33–45 (2003).

Scott, R. W. et al. LIM kinases are required for invasive path generation by tumor and tumor-associated stromal cells. J. Cell Biol. 191, 169–185 (2010).

Mattila, P. K. & Lappalainen, P. Filopodia: molecular architecture and cellular functions. Nature Rev. Mol. Cell Biol. 9, 446–454 (2008).

Chhabra, E. S. & Higgs, H. N. The many faces of actin: matching assembly factors with cellular structures. Nature Cell Biol. 9, 1110–1121 (2007).

Raucher, D. et al. Phosphatidylinositol 4,5-bisphosphate functions as a second messenger that regulates cytoskeleton–plasma membrane adhesion. Cell 100, 221–228 (2000).

Nachmias, V. T., Kavaler, J. & Jacubowitz, S. Reversible association of myosin with the platelet cytoskeleton. Nature 313, 70–72 (1985).

Dikovsky, D., Bianco-Peled, H. & Seliktar, D. Defining the role of matrix compliance and proteolysis in three-dimensional cell spreading and remodeling. Biophys. J. 94, 2914–2925 (2008).

Raucher, D. & Sheetz, M. P. Cell spreading and lamellipodial extension rate is regulated by membrane tension. J. Cell Biol. 148, 127–136 (2000).

Schober, J. M., Komarova, Y. A., Chaga, O. Y., Akhmanova, A. & Borisy, G. G. Microtubule- targeting-dependent reorganization of filopodia. J. Cell Sci. 120, 1235–1244 (2007).

Zaidel-Bar, R., Ballestrem, C., Kam, Z. & Geiger, B. Early molecular events in the assembly of matrix adhesions at the leading edge of migrating cells. J. Cell Sci. 116, 4605–4613 (2003).

Wolfenson, H., Henis, Y. I., Geiger, B. & Bershadsky, A. D. The heel and toe of the cell's foot: a multifaceted approach for understanding the structure and dynamics of focal adhesions. Cell Motil. Cytoskeleton 66, 1017–1029 (2009).

Franz, C. M. & Muller, D. J. Analyzing focal adhesion structure by atomic force microscopy. J. Cell Sci. 118, 5315–5323 (2005).

Bershadsky, A., Chausovsky, A., Becker, E., Lyubimova, A. & Geiger, B. Involvement of microtubules in the control of adhesion-depend ent signal transduction. Curr. Biol. 6, 1279–1289 (1996).

Chellaiah, M. A., Biswas, R. S., Yuen, D., Alvarez, U. M. & Hruska, K. A. Phosphatidylinositol 3, 4, 5-trisphosphate directs association of Src homology 2-containing signaling proteins with gelsolin. J. Biol. Chem. 276, 47434–47444 (2001).

Furlan, F. et al. Urokinase plasminogen activator receptor affects bone homeostasis by regulating osteoblast and osteoclast function. J. Bone Miner. Res. 22, 1387–1396 (2007).

Miyauchi, A. et al. Osteoclast cytosolic calcium, regulated by voltage-gated calcium channels and extracellular calcium, controls podosome assembly and bone resorption. J. Cell Biol. 111, 2543–2552 (1990).

Monsky, W. L. et al. A potential marker protease of invasiveness, seprase, is localized on invadopodia of human malignant melanoma cells. Cancer Res. 54, 5702–5710 (1994).

Nakahara, H. et al. Transmembrane/cytoplasmic domain-mediated membrane type 1-matrix metalloprotease docking to invadopodia is required for cell invasion. Proc. Natl Acad. Sci. USA 94, 7959–7964 (1997).

Sato, T. et al. Identification of the membrane-type matrix metalloproteinase MT1-MMP in osteoclasts. J. Cell Sci. 110, 589–596 (1997).