Focal adhesion kinase as a marker of invasive potential in differentiated human thyroid cancer

Owens, Lewis V.; Xu, Li; Dent, Georgette A.; Yang, Xi; Sturge, Glenn C.; Craven, Rolf J.; Cance, William G.

doi:10.1007/bf02409059

Cited by 195 publications

(139 citation statements)

References 17 publications

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“…By contrast, deletion of FAK in endothelial cells resulted in an increase in apoptosis in vivo, leading to lethality before day 10.5 due to extensive haemorrhaging (Braren et al, 2006). Interestingly, whereas fibroblasts isolated from FAK -/-embryos had defects in migration but not survival, FAK -/-endothelial cells in vivo did not show defects in migration but did undergo apoptosis (Judson et al, 1999;Lark et al, 2003;Lark et al, 2005;Lightfoot et al, 2004;Owens et al, 1995;Owens et al, 1996). Together, these data indicate that how FAK controls cell survival depends very much on cellular origin as well as environmental context.…”

Section: Discussionmentioning

confidence: 95%

FAK engages multiple pathways to maintain survival of fibroblasts and epithelia – differential roles for paxillin and p130Cas

Zouq

Keeble

Lindsay

et al. 2009

Journal of Cell Science

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survival signalling in cell types from distinct embryonic lineages that show differing sensitivities to anoikis. We demonstrate that both fibroblasts and epithelial cells prevent anoikis through FAK activation. We show that FAK activates multiple downstream pathways in order to suppress anoikis. However FAK regulates survival through a more restricted set of pathways in the more anoikis-sensitive epithelial cells. Furthermore, we identify a novel role for paxillin in apoptosis suppression.

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Section: Discussionmentioning

confidence: 95%

FAK engages multiple pathways to maintain survival of fibroblasts and epithelia – differential roles for paxillin and p130Cas

Zouq

Keeble

Lindsay

et al. 2009

Journal of Cell Science

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“…FAK, a 125 kDa nonreceptor tyrosine kinase, is an important regulator of cell survival, invasion, migration, and cell cycle progression (21,22). The overexpression of FAK was observed in a number of human malignant cells, with the degree of overexpression correlating with greater aggressiveness (29). FAK is functionally important in transducing intracellular messages associated with growth factor signaling and cell-extracellular matrix interactions that are tightly related to the formation of cell adhesion complex (30).…”

Section: Discussionmentioning

confidence: 99%

Critical Role of Peroxisome Proliferator-Activated Receptor γ on Anoikis and Invasion of Squamous Cell Carcinoma

Masuda

Wada

Nakajima

et al. 2005

Clinical Cancer Research

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Purpose: Peroxisome proliferator-activated receptor g (PPARg) plays a important role in various physiological functions.We examined whether PPARg is expressed in primary squamous cell carcinoma and lymph node metastasis and whether PPARg is a potential target for tumor therapy. Experimental Design and Results: A high-level expression of PPARg was observed in tumor cells of human primary squamous cell carcinoma, lymph node metastasis, and squamous cell carcinoma cell lines. Treatment with PPARg-specific antagonists, but not agonists, caused apoptotic cell death on squamous cell carcinoma cell lines in a concentration-dependent manner. Small interfering RNA for PPARg also inhibited cell adhesion and growth of squamous cell carcinomas. The phosphorylation of focal adhesion kinase (FAK) was decreased by treatment with PPARg antagonists, and resulted in decreases in phosphorylation of Erk and mitogen-activated protein kinase. Furthermore, PPARg antagonists decreased the adhesion of squamous cell carcinomas into fibronectin-coated plates, indicating the inhibition of interaction between squamous cell carcinomas and fibronectin. Expression of integrin a5, a counter adhesion molecule for fibronectin, was inhibited by the treatment with PPARg antagonists.These results indicate that the decrease in integrin a5 and following inhibition of cell adhesion may cause the inhibition of FAK signaling pathways. PPARg antagonists also strongly inhibited invasion of squamous cell carcinoma via down-regulation of CD151expression. Conclusions: The cell death caused by the PPARg antagonists was a result of direct interference with cell adhesion ''anoikis'' involving intracellular FAK signaling pathways. These results imply a potentially important and novel role for the inhibition of PPARg function via the use of specific antagonists in the treatment of squamous cell carcinoma and the prevention of tumor invasion and metastasis.

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“…The biological importance of FAK-mediated signal transduction is underscored by the fact that this tyrosine kinase plays a fundamental role in embryonic development [11,12] and in the control of cell migration [9,[12][13][14][15][16][17][18][19], cell cycle progression [20] and apoptosis [21][22][23][24]. Furthermore, there is increasing evidence linking overexpression of FAK to the invasive properties of cancer cells [25][26][27][28][29][30][31].…”

Section: Introductionmentioning

confidence: 99%

Differential FAK phosphorylation at Ser-910, Ser-843 and Tyr-397 induced by angiotensin II, LPA and EGF in intestinal epithelial cells

Jiang

Sinnett‐Smith

2007

Cellular Signalling

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A rapid increase in the tyrosine phosphorylation of the non-receptor tyrosine kinase FAK is a prominent early event in fibroblasts stimulated by a variety of signaling molecules. However, a variety of epithelial cells, including intestinal epithelial cells, show a high basal level of tyrosine phosphorylated FAK that is only slightly further increased by addition of G protein-coupled receptors (GPCR) agonists or growth factors. In this study, we determined whether these stimuli could elicit FAK phosphorylation at serine residues, including Ser-910 and Ser-843. Our results show that multiple agonists including angiotensin II (ANGII), lysophosphatidic acid (LPA), phorbol esters and EGF induced a striking stimulation of FAK phosphorylation at Ser-910 in rat intestinal epithelial IEC-18 cells via an ERK-dependent pathway. In striking contrast, none of these stimuli promoted a significant further increase in FAK phosphorylation at Tyr-397 in these cells. These results were extended using cultures of polarized human colonic epithelial T84 cells. We found that either carbachol or EGF promoted a striking ERK-dependent phosphorylation of FAK at Ser-910, but these agonists caused only slight stimulation of FAK at Tyr-397 in T84 cells. In addition, we demonstrated that GPCR agonists also induced a dramatic increase of FAK phosphorylation at Ser-843 in either IEC-18 or T84 cells. Our results indicate that Ser-910 and Ser-843, rather than Tyr-397, are prominent sites differentially phosphorylated in response to neurotransmitters, bioactive lipids, tumor promoters and growth factors in intestinal epithelial cells.

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Focal adhesion kinase as a marker of invasive potential in differentiated human thyroid cancer

Abstract: Overexpression of FAK may be part of a mechanism for invasion and metastasis of thyroid cancer. Furthermore, the levels of p125FAK may serve as a marker of biologic behavior in this disease.

Cited by 195 publications

References 17 publications

FAK engages multiple pathways to maintain survival of fibroblasts and epithelia – differential roles for paxillin and p130Cas

FAK engages multiple pathways to maintain survival of fibroblasts and epithelia – differential roles for paxillin and p130Cas

Critical Role of Peroxisome Proliferator-Activated Receptor γ on Anoikis and Invasion of Squamous Cell Carcinoma

Differential FAK phosphorylation at Ser-910, Ser-843 and Tyr-397 induced by angiotensin II, LPA and EGF in intestinal epithelial cells

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