MicroRNA-488 suppresses cell migration through modulation of the focal adhesion activity during chondrogenic differentiation of chick limb mesenchymal cells

Adherens junctions (AJs) and focal adhesion (FA) complexes are necessary for cell migration and morphogenesis, and for the development, growth, and survival of all metazoans. Vinculin is an essential regulator of both AJs and FAs, where it provides links to the actin cytoskeleton. Phosphatidylinositol 4,5-bisphosphate (PIP2) affects the functions of many targets, including vinculin. Here we report the crystal structure of vinculin in complex with PIP2, which revealed that PIP2 binding alters vinculin structure to direct higher-order oligomerization and suggests that PIP2 and F-actin binding to vinculin are mutually permissive. Forced expression of PIP2-binding–deficient mutants of vinculin in vinculin-null mouse embryonic fibroblasts revealed that PIP2 binding is necessary for maintaining optimal FAs, for organization of actin stress fibers, and for cell migration and spreading. Finally, photobleaching experiments indicated that PIP2 binding is required for the control of vinculin dynamics and turnover in FAs. Thus, through oligomerization, PIP2 directs a transient vinculin sequestration at FAs that is necessary for proper FA function.

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Faculty Opinions recommendation of Integrin-specific signaling pathways controlling focal adhesion formation and cell migration.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1013023.188454 ◽

2003 ◽

Author(s):

Dietmar Vestweber

Keyword(s):

Cell Migration ◽

Signaling Pathways ◽

Focal Adhesion ◽

Adhesion Formation ◽

Focal Adhesion Formation

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Faculty Opinions recommendation of Distinct roles of MLCK and ROCK in the regulation of membrane protrusions and focal adhesion dynamics during cell migration of fibroblasts.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1017296.202454 ◽

2004 ◽

Author(s):

Alan Rick Horwitz

Keyword(s):

Cell Migration ◽

Focal Adhesion ◽

Membrane Protrusions

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Faculty Opinions recommendation of Spatiotemporal feedback between actomyosin and focal-adhesion systems optimizes rapid cell migration.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1033154.496143 ◽

2006 ◽

Author(s):

Thomas Egelhoff

Keyword(s):

Cell Migration ◽

Focal Adhesion

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Progesterone promotes focal adhesion formation and migration in breast cancer cells through induction of protease-activated receptor-1

Journal of Endocrinology ◽

10.1530/joe-11-0310 ◽

2012 ◽

Vol 214 (2) ◽

pp. 165-175 ◽

Cited By ~ 18

Author(s):

Jorge Diaz ◽

Evelyn Aranda ◽

Soledad Henriquez ◽

Marisol Quezada ◽

Estefanía Espinoza ◽

...

Keyword(s):

Breast Cancer ◽

Cell Migration ◽

Cancer Cells ◽

Cancer Cell ◽

Breast Cancer Cell ◽

Focal Adhesion ◽

Breast Cancer Cells ◽

Fiber Formation ◽

Coagulation Cascade ◽

Cancer Cell Migration

Progesterone and progestins have been demonstrated to enhance breast cancer cell migration, although the mechanisms are still not fully understood. The protease-activated receptors (PARs) are a family of membrane receptors that are activated by serine proteases in the blood coagulation cascade. PAR1 (F2R) has been reported to be involved in cancer cell migration and overexpressed in breast cancer. We herein demonstrate that PAR1 mRNA and protein are upregulated by progesterone treatment of the breast cancer cell lines ZR-75 and T47D. This regulation is dependent on the progesterone receptor (PR) but does not require PR phosphorylation at serine 294 or the PR proline-rich region mPRO. The increase in PAR1 mRNA was transient, being present at 3 h and returning to basal levels at 18 h. The addition of a PAR1-activating peptide (aPAR1) to cells treated with progesterone resulted in an increase in focal adhesion (FA) formation as measured by the cellular levels of phosphorylated FA kinase. The combined but not individual treatment of progesterone and aPAR1 also markedly increased stress fiber formation and the migratory capacity of breast cancer cells. In agreement with in vitro findings, data mining from the Oncomine platform revealed that PAR1 expression was significantly upregulated in PR-positive breast tumors. Our observation that PAR1 expression and signal transduction are modulated by progesterone provides new insight into how the progestin component in hormone therapies increases the risk of breast cancer in postmenopausal women.

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Phenotype and chondrogenic differentiation of mesenchymal cells from adipose tissue of different species

Journal of Orthopaedic Research® ◽

10.1002/jor.20898 ◽

2009 ◽

Vol 27 (11) ◽

pp. 1499-1507 ◽

Cited By ~ 47

Author(s):

María José Martínez-Lorenzo ◽

María Royo-Cañas ◽

Elena Alegre-Aguarón ◽

Paula Desportes ◽

Tomás Castiella ◽

...

Keyword(s):

Adipose Tissue ◽

Chondrogenic Differentiation ◽

Mesenchymal Cells

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Mechanical Control of Cell Migration by the Metastasis Suppressor Tetraspanin CD82/KAI1

Cells ◽

10.3390/cells10061545 ◽

2021 ◽

Vol 10 (6) ◽

pp. 1545

Author(s):

Laura Ordas ◽

Luca Costa ◽

Anthony Lozano ◽

Christopher Chevillard ◽

Alexia Calovoulos ◽

...

Keyword(s):

Cell Migration ◽

Cell Surface ◽

Focal Adhesion ◽

Nuclear Translocation ◽

Single Cells ◽

Integral Membrane Protein ◽

Metastasis Suppressor ◽

Dependent Manner ◽

Strong Inhibitor ◽

Caveolin 1

The plasma membrane is a key actor of cell migration. For instance, its tension controls persistent cell migration and cell surface caveolae integrity. Then, caveolae constituents such as caveolin-1 can initiate a mechanotransduction loop that involves actin- and focal adhesion-dependent control of the mechanosensor YAP to finely tune cell migration. Tetraspanin CD82 (also named KAI-1) is an integral membrane protein and a metastasis suppressor. Its expression is lost in many cancers including breast cancer. It is a strong inhibitor of cell migration by a little-known mechanism. We demonstrated here that CD82 controls persistent 2D migration of EGF-induced single cells, stress fibers and focal adhesion sizes and dynamics. Mechanistically, we found that CD82 regulates membrane tension, cell surface caveolae abundance and YAP nuclear translocation in a caveolin-1-dependent manner. Altogether, our data show that CD82 controls 2D cell migration using membrane-driven mechanics involving caveolin and the YAP pathway.

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