only in cells, which are produced to the control vector, or F10 15, but not the mutant F1 9th In addition abolished the inhibition of EGF-induced Src activation of Rap1 F10 15 cells. These results suggest that tyrosine residues 1 9 CAS SD is responsible for mediating EGF-dependent Src-dependent activation of Rap1, the actin reorganization and cell f Promotes metastasis. To AT9283 ridiculed these results Ngern, cells were tested for the FG CAS mutations spontaneous metastasis in vivo. W While EGF stimulates metastasis of cells F10 FG were 15 cells, the mutant 9 F1 metastasize not aware of the EGF and therefore not included in this model. However, the growth of the primary Ren tumor in the two mutant lines in the presence or absence of EGF.
Similarly, expressing WT CAS FG in response to EGF metastases, w While not F1 15th Taken together, these results indicate that EGF. A process of cell migration, to the activation of Src kinases and phosphorylation of specific CAS resulting MK-2206 Rap1 activation initiates h Depends These events in the spontaneous metastasis of pancreatic cancer cells in a manner dependent Ngig result of integrin v5, without influencing the growth of the primary Ren tumor. The specificity This way is the fact that a mediation migration on matrix proteins Such as fibronectin or collagen does not require GEF, Src, or CAS highlighted. Thus, we have two ways of the migration of tumor cells, which may be different on the identified dependence Dependence Src.
Epithelial cancer cells metastasize discussion of a related series of successive steps, the REN for the invasion and remodeling of the extracellular Lead matrix and the mobilization of tumor cells, ultimately. Identification of donors, which is to activate the migration mechanism is essential to understand the spread of tumor cells to secondary Ren locations. In this study, we investigated signaling events by EGF and in particular the integrin invasive behavior of cancer cells found coordinated regulate. There is a growing body of literature with integrins in cancer therapy. Integrin-mediated adhesion Sion leads to intracellular Re signaling pathways that regulate cell survival, proliferation and migration. For example, 4 integrin physically interacts with ErbB2 in breast cancer cells and tr Gt nozzles for initiation, growth and invasion of ErbB2-induced mammary tumors in transgenic M.
In addition, shows the removal of 1-integrin in a transgenic mouse model of mammary tumorigenesis important is that for the initiation of prime Ren tumors and growth through the activation of FAK. Accordingly, the treatment of the cells with an inhibitor of FAK reduced FG cell migration in an integrin 1 and 5 fa Dependent Ngig what shows that FAK is necessary for the general function of the integrin. In contrast, the blocking or reduction of 5-integrin has rtumors not inhibit initiation or growth of the primary But reduce EGFand Src induces metastasis in vivo. Our results indicate that it is. Various paths by integrins in the migration of tumor cells, which differ in terms of their dependence Dependence t itself GEF small GTPases, Src activity And the activation state of the integrin-mediated v5 In the absence of EGF ligation v5 is not sufficient to activate the small GTPases Rac1 and Rap1. In contrast, then ligation of 1 integrin activation Rac1 and Rap1 effected in a manner which is