Dasatinib was recently new U approval for the treatment of myeloid leukemia Mie With imatinib-resistant chronic and is currently being evaluated in clinical trials against solid tumors. Two LY294002 large e substrates active Src kinase, the effect on cell migration focal adhesion kinase and Crk YEARS Ring substrate. FAK promotes f Building multi-protein complexes for the turnover of focal contacts facilitate cell migration and invasion integrinmediated required. After phosphorylation, CAS and Crk recruits DOCK180 that the small GTPase activity coordinate t required for the cell migration and invasion. Src dependent-Dependent phosphorylation of CAS also confers invasive growth potential of transformed cells.
Phosphorylation of the substrate Dom ne of CAS is important for the activation of the small GTPase Rap1 and invasive behavior in vivo, but not tumor growth. Sion cell adhesion At the extracellular Ren matrix f Promotes integrin dependent-Dependent association between Src and FAK. In addition to playing an r The adhesive integrin mediated survival cytosolic Nutlin-3 signaling events incidence of cell proliferation, motility, and t. Integrin activation was confinement in many pathological processes Brought Lich tumor initiation and growth, angiogenesis and metastasis in combination. Furthermore, the integrin-mediated adhesion Sion the signaling pathways by direct phosphorylation of growth factor receptors to improve.
In this study, we have a pathway leading to the spontaneous metastasis of human pancreatic cancer has found no effect on the growth of the primary Ren tumor. We have two different paths of migration of tumor cells, the t in terms of their dependence Dependence mediated by Src kinase GEF activity Differ and the activation of integrin v5. Gives the matrix proteins Such as fibronectin or collagen, cell migration by integrins and 1 does not require Src kinase or EGF. In contrast, EGF and Src activity t for L Solution specific tyrosine phosphorylation in the substrate Dom ne of CAS which to activate Rap1 w During integrin-mediated cell 5 Invasivit t And f metastasis of cancer cells Rdern pancreas without the prim re tumor growth. Sun EGFR SRC appears 5 abh-Dependent way contribute to metastatic properties of pancreatic cancer.
Antique Body inhibitors and methods were purchased from Santa Cruz Biotechnology, Invitrogen, Cell Signaling Technology, Millipore, Sigma and BD Transduction Labs. LM142, P4C10, P1F6 Antique Bodies were prepared as described. The Src inhibitor SKI 606 was used at 500 nM. FAK inhibitor PF-228 was used 1M. CAS mutated cDNA was from templates PRC CASmyc CMV using primers containing EcoR1 and BamH1 sites in the neighborhood of the region encoding the Volll Amplified ngenprotein CAS. Mutated cDNAs were subcloned into pEGFP C1 vector with restriction enzymes EcoR1 and BamH1, and ligated using the Rapid DNA Ligation kit. All cDNA with mutations in the C1 YXXP pEGFR were sequenced to verify the final plasmid constructs. FG Mycoplasma negative human cell carcinoma of the pancreas were cultured in DMEM with 10 FBS. In some experiments, subconfluent cells were transfected with pcDNA3.1 SRCA mutations in pEGFP C1 CAS or the Amaxa Nucleofecto