Abstract 359: C1GALT1 activates multiple RTKs and promotes malignant behaviors in pancreatic adenocarcinoma cells

Abstract

Abstract Pancreatic adenocarcinoma (PDAC), stands up to the 4th in all cancer mortalities and remains the most in progress in America. Curative resection remains the most and only potential strategy but only 15~20% of patients are candidates. Even though, many of them have dismal prognosis. Aberrant glycosylation illustrates an attribution of cancer, especially fot promoting malignant behaviors in adenocarcinomas. Altered expression of glycans, such as GalNAcα1-O-S/T (Tn antigen) and Galβ1,3-GalNAc-S/T (T antigen), is hallmark of cancers. Core 1 β1,3-galactosyltransferase (C1GALT1) catalyzes the transfer of Gal to Tn antigen to form T antigen. C1GALT1 is reported to contribute to clinicopathological features and malignant phenotypes in various cancers. However, the expression and function of C1GALT1 in PDAC remain unrevealed. Our data showed that C1GALT1 was overexpressed in PDAC tissues and correlated with poor prognosis. C1GALT1 knockdown inhibited viability, migration, and invasion analyzed by MTT, transwell migration, and Matrigel invasion assays, respectively, in PDAC cells, associated with increased Tn antigen but decreased T antigen expression. Conversely, C1GALT1 overexpression promoted these malignant behaviors. C1GALT1 knockdown inhibited AKT and ERK activities in PDAC cells. Consistently, phospho-receptor tyrosine kinase (p-RTK) array showed decreased phosphorylation of several RTKs including EGFR, IGF1R, and FLT3. Additionally, flow cytometry of C1GALT1 knockdown cells showed enhanced apoptosis, which was associated with decreased catalase, Bcl-x, and death receptor DR5 revealed by apoptosis array. We also found that C1GALT1 knockdown arrested G1 progression in PDAC cells. Furthermore, gene set enrichment analysis of cDNA microarray indicated that C1GALT1 regulated cell cycle, cytoskeleton, and chromatin structure in PDAC cells. These findings indicate that higher C1GALT1 expression predicts worse survival of PDAC and enhances malignant characters in PDAC cells, highlighting a fundamental role of C1GALT1 in PDAC development. Note: This abstract was not presented at the meeting. Citation Format: Ting-Chun Kuo, Hsueh-Fen Juan, Yu-Wen Tien, Min-Chuan Huang. C1GALT1 activates multiple RTKs and promotes malignant behaviors in pancreatic adenocarcinoma cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 359. doi:10.1158/1538-7445.AM2017-359