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Related Concept Videos

Cancer Cell Migration through Invadopodia01:35

Cancer Cell Migration through Invadopodia

Invadosome is a broad category of cell surface structures with proteolytic activity that  degrades the extracellular matrix (ECM). Invadosomes are present in normal cell types, including macrophages, endothelial cells, and neurons, as well as tumor cells. Although the macrophage podosomes and tumor cell invadopodia are classified as invadosomes, they have different structures, molecular pathways, and functions. Podosomes are short structures that last for a few minutes. However, invadopodia can...
Cell-matrix's Response to Mechanical Forces01:13

Cell-matrix's Response to Mechanical Forces

In animal cells, the extracellular matrix allows cells within tissues to withstand external stresses and transmits signals from the outside of the cell to the inside. The extracellular matrix is extensive, and its composition varies between different types of tissues. For example, the reticular fibers and ground substance make up the ECM in loose connective tissue, while collagen and bone minerals make up the ECM of bone tissue. 
Anchoring junctions mechanically attach a cell to the...
Mechanism of Lamellipodia Formation01:31

Mechanism of Lamellipodia Formation

Cells migrating in response to external stimuli form lamellipodia, which are thin membrane protrusions supported by a mesh of linked, branched, or unbranched actin filaments. These actin filaments interact with myosin motor proteins, creating the dynamic actomyosin complex within the cytoskeleton. Contractility, or the ability to generate contractile stress, is inherent to the actomyosin complex. It helps cells detect the stiffness of the surrounding ECM and exert contractile force for...
Mechanism of Filopodia Formation01:39

Mechanism of Filopodia Formation

Filopodia are thin, actin-rich cellular protrusions that play an important role in many fundamental cellular functions. They vary in their occurrence, length, and positioning in different cell types, suggesting their diverse roles.
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Cell Motility through Blebbing01:16

Cell Motility through Blebbing

Blebs are a type of membrane protrusion formed by the internal hydrostatic pressure of the cytoplasm. Blebs are observed in several cell types, including fibroblasts, immune cells, and single-celled organisms like the amoeba. The primary function of blebs is cell locomotion and apoptosis, but they are also found during necrosis and cell division. The life cycle of a bleb comprises an initiation phase followed by the expansion and retraction phases.
Blebbing Through the Matrix
In multicellular...
Intracellular Signaling Affects Focal Adhesions01:17

Intracellular Signaling Affects Focal Adhesions

Integrins act both as extracellular input receivers and as intracellular processing activators. As their name suggests, integrins are entirely integrated into the membrane structure. Their hydrophobic membrane-spanning regions interact with the phospholipid bilayer's hydrophobic region. These membrane receptors provide extracellular attachment sites for effectors like hormones and growth factors. They activate intracellular response cascades when their effectors are bound and active.
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Polyacrylamide Gels for Invadopodia and Traction Force Assays on Cancer Cells
08:48

Polyacrylamide Gels for Invadopodia and Traction Force Assays on Cancer Cells

Published on: January 4, 2015

Extracellular matrix rigidity promotes invadopodia activity.

Nelson R Alexander1, Kevin M Branch1, Aron Parekh1

  • 1Department of Cancer Biology, Vanderbilt University, Nashville, TN 37232, USA.

Current Biology : CB
|August 23, 2008
PubMed
Summary
This summary is machine-generated.

Extracellular matrix (ECM) rigidity directly boosts cancer cell invadopodia activity and numbers. This process involves the cellular contractile apparatus, myosin II, and mechanosensing proteins focal adhesion kinase (FAK) and p130Cas (Cas).

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2D and 3D Matrices to Study Linear Invadosome Formation and Activity
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Polyacrylamide Gels for Invadopodia and Traction Force Assays on Cancer Cells
08:48

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Published on: January 4, 2015

Quantitative Measurement of Invadopodia-mediated Extracellular Matrix Proteolysis in Single and Multicellular Contexts
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Published on: August 27, 2012

2D and 3D Matrices to Study Linear Invadosome Formation and Activity
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2D and 3D Matrices to Study Linear Invadosome Formation and Activity

Published on: June 2, 2017

Area of Science:

  • Cell Biology
  • Cancer Research
  • Biophysics

Background:

  • Invadopodia are actin-rich structures cancer cells use to degrade the extracellular matrix (ECM).
  • While similar structures exist in other cells (podosomes), their function differs.
  • The regulation of invadopodia by physical ECM cues remains largely unknown.

Purpose of the Study:

  • To investigate whether ECM rigidity influences invadopodia function in cancer cells.
  • To elucidate the molecular pathways involved in sensing and responding to ECM rigidity.

Main Methods:

  • Utilized polyacrylamide substrates of varying rigidity to culture cancer cells.
  • Inhibited key components of the cellular contractile apparatus (nonmuscle myosin II, myosin light chain kinase, Rho kinase).
  • Assessed invadopodia number and activity (ECM degradation) using microscopy and biochemical assays; analyzed protein localization and phosphorylation (p130Cas, FAK).

Main Results:

  • ECM rigidity directly increased both the number and degradative activity of invadopodia.
  • Inhibition of nonmuscle myosin II, myosin light chain kinase, or Rho kinase abolished invadopodia-associated ECM degradation.
  • Active, phosphorylated forms of p130Cas (Cas) and focal adhesion kinase (FAK) were found in actively degrading invadopodia and were sensitive to myosin inhibitors.

Conclusions:

  • ECM rigidity enhances invadopodia-driven matrix degradation in invasive cancer cells.
  • A signaling pathway involving the cellular contractile apparatus, myosin II, and mechanosensors FAK/Cas mediates this response.
  • This mechanism may explain the link between tissue density and cancer aggressiveness.