Taken together, these results indicate that the activation of Src sufficient MGCD0103 auszul Sen cell migration v5 dependent Ngig is. We then examined whether activated Src sufficient to induce spontaneous metastasis of FG cells was. FG cells or those expressing SRCA were implanted on the CAM of 10 day old chick embryos and left primary form Rtumoren and spontaneous lung metastases. W While erh Hte Src kinase activity T has no effect on the growth of the primary Ren tumor, it was sufficient to induce lung metastases. To r Evaluate V5 of the process, the tumor-bearing animals were injected systemically with a barrier function or function nonblocking Antique Body against Integrin v5.
Completely blocking integrin function Inhibited constantly embroidered v5 SRCA induced metastasis l levels. Especially erh Ht Src activity T or blocking the function GDC-0941 v5 has no influence on the growth of prime Ren tumors. These results indicate that activation of the Src kinase is, in combination with necessary and sufficient for v5 spontaneous metastases. Since the activation of EGFR Src v5 initiated FG pancreatic carcinoma cell migration by in vitro and in vivo, we give if would pronounced Gte histological origin of carcinomas vitronectin migrate in response to the activation of integrin 5, EGF and Src. As for MCF FG 7 breast cancer cells and other tumor cell lines was observed that their primary cellular Re v5 express vitronectin receptor inducible GEF, Src-mediated Ren response to a selective migration resulted vitronectin.
Additionally Tzlich, as for FG cells observed, EGF-induced cell migration, MCF-7 breast cancer cells to vitronectin selectively 5-integrin function is required. Taken together, these results provide an r Src for modules 5 signaling in several cancers. EGF induced migration depends v5-Dependent in vitro and in vivo metastasis Srcmediated requires phosphorylation of a specific region in the substrate Dom ne of CAS to the mechanism by which EGF mediated Src activity T leads to an increased FITTINGS metastasis, cell lysates stimulated by EGF investigate FG in the presence or absence of an inhibitor of Src with anti phosphotyrosine Src substrates were probed to identify relevant. As expected, the results in the EGF stimulation of phosphorylation of EGFR to about 175 kD, as well as other proteins.
By inhibition of Src, showed a number of these proteins A marked decrease in tyrosine phosphorylation, especially a set of phosphorylated bands in the range of 120 140 kD. Previous studies have suggested that FAK and CAS protein stimulates phospho important in this size Enbereich for FG cells by EGF. Src activity t Tr # adds to the phosphorylation of FAK at Y576, Y577, Y861, Y925 and Y397 is a place while the autophosphorylation of FAK. In cells stimulated by EGF FG, phosphorylation of FAK Y397 not over the background levels obtained Ht. Pharmacological inhibition of FAK Y397 reduced autophosphorylation and EGF-induced phosphorylation of Y861 and the EGF-induced migration on vitronectin broke v5 mediation and mediation a migration on fibronectin. These results show that FAK plays an r Wildcard in the migration of cells on multiple substrates. As N Chstes we investigated whether EGF stimulation dependent Src phosphorylation could lead O-dependent