The residence time of focal adhesion kinase (FAK) and paxillin at focal adhesions in renal epithelial cells is determined by adhesion size, strength and life cycle status.

Dévédec, Sylvia E. Le; Geverts, Bart; Bont, Hans de; Yan, Kuan; Verbeek, Fons J.; Houtsmuller, Adriaan B.; Water, Bob van de

doi:10.1242/jcs.104273

Cited by 29 publications

(34 citation statements)

References 43 publications

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“…New findings show that CPT increases PAX expression and appears to do so in a concentration-dependent manner ( Figure 4A). The increase in PAX could be strengthening the focal adhesion contacts [8,50] and cytoskeletal stability as has been observed in epithelial cells [51,52] and migration [9,53], thereby reducing capacity of these cells to move in response to a stimulant. In complement, FAK and Src together act as a signaling nexus to induce phosphorylation of FA proteins including autophosphorylation of FAK itself, PAX and p130Cas [4,6,54].…”

Section: Discussionmentioning

confidence: 86%

Exchange protein activated by cAMP (EPAC) controls migration of vascular smooth muscle cells in concentration- and timedependent manner

Adderley¹,

Martin²,

Tulis³

2015

Arch Physiol

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Section: Discussionmentioning

confidence: 86%

Exchange protein activated by cAMP (EPAC) controls migration of vascular smooth muscle cells in concentration- and timedependent manner

Adderley¹,

Martin²,

Tulis³

2015

Arch Physiol

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“…7). Adhesion size has been found to correlate with residence times of FAK and PAX within focal contacts (14). This indicates slower focal adhesion dynamics in larger adhesions and, therefore, more sustained attachment than in smaller adhesion sites, which have been suggested to represent less mature, more transient contacts to the substrate.…”

Section: Discussionmentioning

confidence: 98%

Myoferlin depletion elevates focal adhesion kinase and paxillin phosphorylation and enhances cell-matrix adhesion in breast cancer cells

Blackstone

Ackerman

et al. 2015

American Journal of Physiology-Cell Physiology

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Blackstone BN, Li R, Ackerman WE 4th, Ghadiali SN, Powell HM, Kniss DA. Myoferlin depletion elevates focal adhesion kinase and paxillin phosphorylation and enhances cell-matrix adhesion in breast cancer cells. Am J Physiol Cell Physiol 308: C642-C649, 2015. First published January 28, 2015; doi:10.1152/ajpcell.00276.2014.-Breast cancer is the second leading cause of malignant death among women. A crucial feature of metastatic cancers is their propensity to lose adhesion to the underlying basement membrane as they transition to a motile phenotype and invade surrounding tissue. Attachment to the extracellular matrix is mediated by a complex of adhesion proteins, including integrins, signaling molecules, actin and actin-binding proteins, and scaffolding proteins. Focal adhesion kinase (FAK) is pivotal for the organization of focal contacts and maturation into focal adhesions, and disruption of this process is a hallmark of early cancer invasive potential. Our recent work has revealed that myoferlin (MYOF) mediates breast tumor cell motility and invasive phenotype.In this study we demonstrate that noninvasive breast cancer cell lines exhibit increased cell-substrate adhesion and that silencing of MYOF using RNAi in the highly invasive human breast cancer cell line MDA-MB-231 also enhances cell-substrate adhesion. In addition, we detected elevated tyrosine phosphorylation of FAK (FAK Y397 ) and paxillin (PAX Y118 ), markers of focal adhesion protein activation. Morphometric analysis of PAX expression revealed that RNAi-mediated depletion of MYOF resulted in larger, more elongated focal adhesions, in contrast to cells transduced with a control virus (MDA-231 LVC cells), which exhibited smaller focal contacts. Finally, MYOF silencing in MDA-MB-231 cells exhibited a more elaborate ventral cytoskeletal structure near focal adhesions, typified by pronounced actin stress fibers. These data support the hypothesis that MYOF regulates cell adhesions and cell-substrate adhesion strength and may account for the high degree of motility in invasive breast cancer cells. myoferlin; breast cancer; cell adhesion; cell motility; cell mechanics CELL-SUBSTRATUM AND CELL-CELL adhesion is a fundamental biological process required for the development and function of metazoans. Adhesion of cells to their underlying extracellular matrix (ECM) is mediated largely by integrins acting as specific receptors for proteins in the basal lamina, e.g., collagen IV, fibronection, and laminin (1, 31). Integrin engagement activates a cascade of phosphorylation events in a number of adhesion proteins, culminating in strengthening of attachment forces through the actin cytoskeleton (18,21,31). Disruption of cell-matrix attachment is a hallmark feature of most carcinomas (8). In these cancers, cells within epithelial structures, e.g., mammary acini and ducts, proliferate abnormally, lose cell-cell contact, and detach from the subjacent basal lamina to initiate migration and invasion into the surrounding stroma and subsequently metastasize to distant sites, ...

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“…As one of the downstream regulatory proteins of focal adhesion kinase (FAK), paxillin is able to control cell metastasis and migration (9). Paxillin is closely associated with the mitogen activated protein kinase (MAPK)/FAK signaling pathway, since paxillin and FAK are required for the MAPK/FAK signaling pathway to regulate the adhesion process of fibroblasts.…”

Section: Introductionmentioning

confidence: 99%

Anticancer effect of docetaxel induces apoptosis of prostate cancer via the cofilin-1 and paxillin signaling pathway

Xiao

Chun-wen

et al. 2016

Molecular Medicine Reports

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Prostate cancer is a common multiple malignant tumor occurring in males. Prostate cancer mortality is the 2nd most common of all tumor types in Western countries and the mortality of morbidity is 13% in the USA. The present study aimed to investigate the anticancer effect of docetaxel on inducing the apoptosis of prostate cancer via the cofilin‑1 and paxillin signaling pathway. Treatment with docetaxel (1‑50 nM) disposed the human LNCaP prostate cancer cells for 24 h. Cell growth and cytotoxicity were subsequently measured using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and lactate dehydrogenase assay, respectively. Docetaxel-induced cell death was analyzed using flow cytometric and caspase-3 assays. Reverse transcription‑quantitative polymerase chain reaction analysis was used to detect the gene expression of cofilin‑1 and western blots were used to determine the protein expression of paxillin. Treatment with docetaxel inhibited cell growth, promoted cytotoxicity, activated apoptosis and increased caspase‑3 activity in the LNCaP cells. Notably, administration of docetaxel reduced the gene expression of cofilin‑1 and the protein expression of paxillin in the LNCaP cells. Additionally, knockdown of cofilin‑1 advanced the anticancer effect of docetaxel against LNCaP cells through suppression of the paxillin pathway. The present findings demonstrated that the anticancer effect of docetaxel induces the apoptosis of prostate cancer via the suppression of the cofilin‑1 and paxillin signaling pathways, which will assist in setting a stage for the clinical treatment of prostate cancer.

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The residence time of focal adhesion kinase (FAK) and paxillin at focal adhesions in renal epithelial cells is determined by adhesion size, strength and life cycle status.

Cited by 29 publications

References 43 publications

Exchange protein activated by cAMP (EPAC) controls migration of vascular smooth muscle cells in concentration- and timedependent manner

Exchange protein activated by cAMP (EPAC) controls migration of vascular smooth muscle cells in concentration- and timedependent manner

Myoferlin depletion elevates focal adhesion kinase and paxillin phosphorylation and enhances cell-matrix adhesion in breast cancer cells

Anticancer effect of docetaxel induces apoptosis of prostate cancer via the cofilin-1 and paxillin signaling pathway

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