The Activated Insulin-Like Growth Factor I Receptor Induces Depolarization in Breast Epithelial Cells Characterized by Actin Filament Disassembly and Tyrosine Dephosphorylation of FAK, Cas, and Paxillin

Guvakova, Marina A.; Surmacz, Ewa

doi:10.1006/excr.1999.4566

Cited by 74 publications

(63 citation statements)

References 43 publications

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“…IGF1R signaling has been famous for mediating anti-apoptotic and mitogenic effects via PI3K/PKB and Ras/MAPK pathways. Yet, IGF1R also modulates cellsubstrate adhesion, migration, invasion and cell-cell interaction by signaling via FAK [112,113]. IGF1R has also been shown to modulate the expression and function of different junctional proteins, including cadherins, catenins, ZO-1 and the small GTPases RhoA, Rac1 and Cdc42 [114].…”

Section: Signals Elicited By Erbb Receptorsmentioning

confidence: 99%

Metastasis: cell-autonomous mechanisms versus contributions by the tumor microenvironment

Kopfstein

Christofori

2006

Cell. Mol. Life Sci.

209

160

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Abstract. The fatality of cancer predominantly results from the dissemination of primary tumor cells to distant sites and the subsequent formation of metastases. During tumor progression, some of the primary tumor cells as well as the tumor microenvironment undergo characteristic molecular changes, which are essential for the metastatic dissemination of tumor cells. In this review, we will discuss recent insights into pro-metastatic events occurring in tumor cells themselves and in the tumor stroma. Tumor cell-intrinsic alterations include the loss of cell polarity and alterations in cell-cell and cell-matrix Cell. Mol. Life Sci. 63 (2006) 449-468 1420-682X/06/040449-20 DOI 10.1007/s00018-005-5296-8 © Birkhäuser Verlag, Basel, 2006 adhesion as well as deregulated receptor kinase signaling, which together support detachment, migration and invasion of tumor cells. On the other hand, the tumor stroma, including endothelial cells, fibroblasts and cells of the immune system, is engaged in an active molecular crosstalk within the tumor microenvironment. Subsequent activation of blood vessel and lymph vessel angiogenesis together with inflammatory and immune-suppressive responses further promotes cancer cell migration and invasion, as well as initiation of the metastatic process.

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Section: Signals Elicited By Erbb Receptorsmentioning

confidence: 99%

Metastasis: cell-autonomous mechanisms versus contributions by the tumor microenvironment

Kopfstein

Christofori

2006

Cell. Mol. Life Sci.

209

160

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“…Increasing evidence indicates that IGF-I signaling is also pivotal to cell motility and invasion (LeRoith and Roberts, 2003). IGF-I-induced cell motility has been characterized in various cell types (Kadowaki et al, 1986;Leventhal et al, 1997;Guvakova and Surmacz, 1999). The earliest detectable morphological change induced by IGF-I is the reorganization of the actin cytoskeleton associated with the formation of lamellipodia (Kadowaki et al, 1986;Leventhal et al, 1997;Guvakova and Surmacz, 1999).…”

Section: Introductionmentioning

confidence: 99%

“…IGF-I-induced cell motility has been characterized in various cell types (Kadowaki et al, 1986;Leventhal et al, 1997;Guvakova and Surmacz, 1999). The earliest detectable morphological change induced by IGF-I is the reorganization of the actin cytoskeleton associated with the formation of lamellipodia (Kadowaki et al, 1986;Leventhal et al, 1997;Guvakova and Surmacz, 1999). Activation of the phosphatidylinositol 3 0 -kinase pathway by IGF-I is essential for this process, which is regulated through focal adhesion proteins, such as focal adhesion kinase (FAK), paxillin and p130 Cas (Kadowaki et al, 1986;Leventhal et al, 1997;Guvakova and Surmacz, 1999).…”

Section: Introductionmentioning

confidence: 99%

“…The earliest detectable morphological change induced by IGF-I is the reorganization of the actin cytoskeleton associated with the formation of lamellipodia (Kadowaki et al, 1986;Leventhal et al, 1997;Guvakova and Surmacz, 1999). Activation of the phosphatidylinositol 3 0 -kinase pathway by IGF-I is essential for this process, which is regulated through focal adhesion proteins, such as focal adhesion kinase (FAK), paxillin and p130 Cas (Kadowaki et al, 1986;Leventhal et al, 1997;Guvakova and Surmacz, 1999). IGF-I induces rapid tyrosine phosphorylation of FAK, paxillin and p130 Cas in human neuroblastoma cells (SH-SY5Y) and Swiss 3T3 cells (Leventhal et al, 1997;Guvakova and Surmacz, 1999), although disputation exists (Konstantopoulos and Clark, 1996;Casamassima and Rozengurt, 1998).…”

Section: Introductionmentioning

confidence: 99%

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Rapamycin inhibits F-actin reorganization and phosphorylation of focal adhesion proteins

et al. 2008

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“…To explore the mechanism and significance of FAK dephosphorylation by DCA, we treated HCA-7 cells with phenylarsine oxide (PAO), an inhibitor of protein tyrosine phosphatases (PTPases) (23). Cells were then treated with DCA (100 M) for the indicated times.…”

Section: Fak Localizes To Focal Adhesionsmentioning

confidence: 99%

Deoxycholic acid differentially regulates focal adhesion kinase phosphorylation: role of tyrosine phosphatase ShP2

Khare¹,

Holgren²,

Samarel³

2006

American Journal of Physiology-Gastrointestinal and Liver Physi

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Khare S, Holgren C, Samarel AM. Deoxycholic acid differentially regulates focal adhesion kinase phosphorylation: role of tyrosine phosphatase ShP2. Am J Physiol Gastrointest Liver Physiol 291: G1100 -G1112, 2006. First published August 17, 2006 doi:10.1152/ajpgi.00008.2006.-Environmental factors, including dietary fats, are implicated in colonic carcinogenesis. Dietary fats modulate secondary bile acids including deoxycholic acid (DCA) concentrations in the colon, which are thought to contribute to the nutritional-related component of colon cancer risk. Here we demonstrate, for the first time, that DCA differentially regulated the sitespecific phosphorylation of focal adhesion kinase (FAK). DCA decreased adhesion of HCA-7 cells to the substratum and induced dephosphorylation of FAK at tyrosine-576/577 (Tyr-576/577) and Tyr-925. Tyrosine phosphorylation of FAK at Tyr-397 remained unaffected by DCA stimulation. Interestingly, we found that c-Src was constitutively associated with FAK and DCA actually activated Src, despite no change in FAK-397 and an inhibition of FAK-576 phosphorylation. DCA concomitantly and significantly increased association of tyrosine phosphatase ShP2 with FAK. Incubation of immunoprecipitated FAK, in vitro, with glutathione-S-transferaseShP2 fusion protein resulted in tyrosine dephosphorylation of FAK in a concentration-dependent manner. Antisense oligodeoxynucleotides directed against ShP2 decreased ShP2 protein levels and attenuated DCA-induced FAK dephosphorylation. Inhibition of FAK by adenoviral-mediated overexpression of FAK-related nonkinase and gene silencing of Shp2 both abolished DCA's effect on cell adhesion, thus providing a possible mechanism for inside-out signaling by DCA in colon cancer cells. Our results suggest that DCA differentially regulates focal adhesion complexes and that tyrosine phosphatase ShP2 has a role in DCA signaling.

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The Activated Insulin-Like Growth Factor I Receptor Induces Depolarization in Breast Epithelial Cells Characterized by Actin Filament Disassembly and Tyrosine Dephosphorylation of FAK, Cas, and Paxillin

Cited by 74 publications

References 43 publications

Metastasis: cell-autonomous mechanisms versus contributions by the tumor microenvironment

Metastasis: cell-autonomous mechanisms versus contributions by the tumor microenvironment

Rapamycin inhibits F-actin reorganization and phosphorylation of focal adhesion proteins

Deoxycholic acid differentially regulates focal adhesion kinase phosphorylation: role of tyrosine phosphatase ShP2

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