An integrin alpha(v)beta(3)-c-Src oncogenic unit promotes anchorage-independence and tumor progression. Export

@article{citeulike:5846930, abstract = {Integrins regulate adhesion-dependent growth, survival and invasion of tumor cells. In particular, expression of integrin alpha(v)beta(3) is associated with progression of a variety of human tumors. Here we reveal a previously undescribed adhesion-independent role for integrin alpha(v)beta(3) in pancreatic cancer and other carcinomas. Specifically, alpha(v)beta(3) expressed in carcinoma cells enhanced anchorage-independent tumor growth in vitro and increased lymph node metastases in vivo. These effects required recruitment of c-Src to the beta(3) integrin cytoplasmic tail, leading to c-Src activation, Crk-associated substrate (CAS) phosphorylation and tumor cell survival that, unexpectedly, was independent of cell adhesion or focal adhesion kinase (FAK) activation. Pharmacological blockade of c-Src kinase activity or decreased expression of endogenous alpha(v)beta(3) integrin or c-Src not only inhibited anchorage-independent growth but also suppressed metastasis in vivo, yet these manipulations did not affect tumor cell migration or invasion. These data define an unexpected role for an integrin as a mediator of anchorage independence, suggesting that an alpha(v)beta(3)-c-Src signaling module may account for the aggressive behavior of integrin alpha(v)beta(3)-expressing tumors in humans.}, author = {Desgrosellier, Jay S. and Barnes, Leo A. and Shields, David J. and Huang, Miller and Lau, Steven K. and Pr\'{e}vost, Nicolas and Tarin, David and Shattil, Sanford J. and Cheresh, David A.}, citeulike-article-id = {5846930}, citeulike-linkout-0 = {http://dx.doi.org/10.1038/nm.2009}, citeulike-linkout-1 = {http://view.ncbi.nlm.nih.gov/pubmed/19734908}, citeulike-linkout-2 = {http://www.hubmed.org/display.cgi?uids=19734908}, day = {6}, doi = {10.1038/nm.2009}, issn = {1546-170X}, journal = {Nature medicine}, keywords = {beta3, cancer}, month = {September}, posted-at = {2009-09-28 13:18:07}, priority = {2}, title = {An integrin alpha(v)beta(3)-c-Src oncogenic unit promotes anchorage-independence and tumor progression.}, url = {http://dx.doi.org/10.1038/nm.2009}, year = {2009} }

TY - JOUR ID - citeulike:5846930 L3 - citeulike-article-id:5846930 N2 - Integrins regulate adhesion-dependent growth, survival and invasion of tumor cells. In particular, expression of integrin alpha(v)beta(3) is associated with progression of a variety of human tumors. Here we reveal a previously undescribed adhesion-independent role for integrin alpha(v)beta(3) in pancreatic cancer and other carcinomas. Specifically, alpha(v)beta(3) expressed in carcinoma cells enhanced anchorage-independent tumor growth in vitro and increased lymph node metastases in vivo. These effects required recruitment of c-Src to the beta(3) integrin cytoplasmic tail, leading to c-Src activation, Crk-associated substrate (CAS) phosphorylation and tumor cell survival that, unexpectedly, was independent of cell adhesion or focal adhesion kinase (FAK) activation. Pharmacological blockade of c-Src kinase activity or decreased expression of endogenous alpha(v)beta(3) integrin or c-Src not only inhibited anchorage-independent growth but also suppressed metastasis in vivo, yet these manipulations did not affect tumor cell migration or invasion. These data define an unexpected role for an integrin as a mediator of anchorage independence, suggesting that an alpha(v)beta(3)-c-Src signaling module may account for the aggressive behavior of integrin alpha(v)beta(3)-expressing tumors in humans. JF - Nature medicine SN - 1546-170X TI - An integrin alpha(v)beta(3)-c-Src oncogenic unit promotes anchorage-independence and tumor progression. KW - beta3 KW - cancer AU - Desgrosellier, Jay AU - Barnes, Leo AU - Shields, David AU - Huang, Miller AU - Lau, Steven AU - Prévost, Nicolas AU - Tarin, David AU - Shattil, Sanford AU - Cheresh, David PY - 2009/09/06/ UR - http://dx.doi.org/10.1038/nm.2009 ER -