Abstract 1640: SORBS1-related multiprotein complex regulates metastasis of cancer

Purpose: CAP (Cbl-associated protein), also known as Sorbin and SH3 domain-containing protein 1 is encoded by the SORBS1 gene. These proteins contain a conserved sorbin homology (SOHO) domain and three SH3 domains. CAP is an adaptor protein that has been associated with the actin cytoskeleton, signaling through receptor tyrosine kinases and cell adhesion. Although, CAP is proven to have many known functions, this protein is only reported in specific field of signaling pathway. Cell adhesion and actin dynamics which have been supposed to participate in CAP are crucial factors of cancer metastasis. The role of CAP has been described in the literature, although their specific roles remain to be clarified in cancer. Methods and materials: Colorectal cancer cell lines were transduced by lentivirus containing shRNA plasmid (shSORBS1 plasmid). To elucidate function of SORBS1 as regulator of cancer metastasis, western blotting, cell migration assay and immunoprecipitation assays were performed. Conclusion: According to the several reports of SORBS1 function, phosphorylation of ERK and mTOR was identified. Although ERK phosphorylation were not changed in normal condition, there were different aspects between control group and SORBS1 knockdown group with insulin treatment. Moreover, mTOR phosphorylation of SORBS1 knockdown group was less in the control group than in the normal condition. Immunoprecipitation of SORBS1 was performed to search for the binding compounds. We chose the AHNAK protein as the convincing candidate protein related with SORBS1. Several studies reported that AHNAK protein is related to proliferation and EMT by binding of specific signaling molecules. Indeed, there were remarkable differences of invasiveness ability between control group and knockdown group. Citation Format: Woo-Cheol Cho, Ja-Lok Ku. SORBS1-related multiprotein complex regulates metastasis of cancer. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1640.