Abstract 5098: Participation of Crk-associated substrate (CAS) in human pancreatic cancer cell migration, invasion and metastatic processes

Abstract

Abstract Introduction; Crk-associated substrate (CAS, p130Cas) is a major tyrosine phosphorylated protein in cells transformed by v-crk and v-src oncogenes. In non-transformed cells, CAS localizes to focal adhesions and undergoes tyrosine phosphorylation in response to integrin-mediated signaling. In the current study, we evaluate the role of CAS in cell migration, invasion and metastatic processes in human pancreatic cancer cells. Materials and Methods; We investigated that CAS tyrosine kinase activity and tumor cell migration, invasion to endothelial cell monolayer in human pancreatic cancer cell lines, in vitro. CAS tyrosine phosphorylation were measured by immunoblotting and immunoprecipitation using anti-CAS monoclonal antibody and anti-phosphotyrosine antibody. Tumor cell migration was measured with Matrigel-coated modified-Boyden's chamber assay. Tumor cell invasion to endothelial cell monolayer was assayed with a co-culture invasion bioassay. Results; Tyrosine phosphorylation of CAS in human pancreatic cancer cells were induced during tumor cell migration and invasion. Phosphorylated tyrosine level of CAS was coincident with invasion capability in human pancreatic cancer cell lines, PSN-1, MiaPacaII, Panc1, despite of similar protein expression level. Protein tyrosine kinase inhibitor, Herbimycin A, had an inhibitory effect on migration and invasion as well as CAS tyrosine phosphorylation in tumor cells. Conclusion; These results indicated that CAS tyrosine phosphorylation in pancreatic tumor cells was correlated with invasive capability, suggesting a pivotal role of CAS in migration, invasion and metastatic processes. Citation Format: Hirotaka Okamoto, Hideki Fujii. Participation of Crk-associated substrate (CAS) in human pancreatic cancer cell migration, invasion and metastatic processes. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 5098. doi:10.1158/1538-7445.AM2015-5098