Abstract 259: Novel biliary tract cancer stem cell biomarker TAGLN2 regulates migration via c-met signaling cascades in biliary tract cancer cells.

Abstract

Abstract Background/Aims : Biliary tract cancer is one of the lethal malignancy. Most biliary tract cancer is diagnosed at advanced stages and have poor prognosis. Currently, there are no standard biomarkers and chemotherapeutic agents for biliary tract cancers. In order to find the biomarkers and therapeutic targets for biliary tract cancer, we have focused on the cancer stem cells (CSCs) with tumor initiating/self renewing/metastatic capacity and chemo/radio-resistance. In this study, we investigated the function of biliary tract CSC related biomarker TALGN2 discovered from comparision of cDNA microarray between sphere and adherent cell populations of biliary tract cancer cell lines. Methods : Analysis using cDNA microarray between sphere and adherent cell populations and selection of CSC specific biomarkers were performed. Among them, we selected TAGLN2 as a biliary CSC related gene. TAGLN2 expression was confirmed by RT-PCR, western blot and immunohistochemistry. To evaluate the function of TAGLN2 in biliary carcinogenesis, we performed targeted knockdown via siRNA in SNU1196 biliary tract cancer cell line. Results : The expression of stemness and c-met signaling cascades were up-regulated in sphere cells compared with adherent cells. TAGLN2 was also up-regulated in sphere cells. TAGLN2 was highly expressed in most of biliary tract cancer cell lines and biliary tract cancer tissues. TAGLN2 knockdown cells showed decreased cell migration and increased chemosentitivity compared with mock cells. In addition, we found that c-met signaling cascades including PI3K and MAPK were inactivated in TAGLN2 knockdown cells. Conclusions : These results suggest that biliary tract CSC biomarker TAGLN2 is implicated in biliary tract cancer progression and TAGLN2 may be a potential biomarker and therapeutic target for biliary tract cancer. Citation Format: Soo Been Park, Sun A Kim, Si Young Song. Novel biliary tract cancer stem cell biomarker TAGLN2 regulates migration via c-met signaling cascades in biliary tract cancer cells. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 259. doi:10.1158/1538-7445.AM2013-259