Abstract 1029: Rab1A and Rab1B promote esophageal squamous cell carcinoma through activating mTORC1 signaling and inhibiting autophagy

Abstract Background: Rab1A has recently been shown to act as an oncogene and promote colorectal and liver tumorigenesis. In this study, we aim to understand the potential role of Rab1A and its homolog Rab1B in esophageal squamous cell carcinoma (ESCC) and the underlying molecular mechanisms. Methods: The expressions of Rab1A and Rab1B in139 paired human ESCC tissues and adjacent normal tissues were evaluated by immunohistochemistry. A series of in vitro and in vivo assays were performed to elucidate the biological functions of Rab1A and Rab1B, and their role in the regulation of mTOR signaling, autophagy and ESCC tumorigenesis. Results: The level of Rab1A and Rab1B is elevated in ESCC tissues, which is positively correlated with tumor TNM stages and N stages. The overall expression of Rab1A and Rab1B is an independent predictor of patient survival (P<0.01). Down-regulation of Rab1A and Rab1B individually and in combination in ESCC cells inhibits cell proliferation and migration, and enhances autophagy. Mechanistically, Rab1A and Rab1B activate mTORC1 to enhance growth and suppress autophagy. Conclusion: Our results suggest that Rab1A and Rab1B cooperatively regulate ESCC proliferation and autophagy by activating mTORC1 signaling. They may serve as promising prognostic biomarkers and/or potential molecular targets of ESCC treatments. Citation Format: Xian-Zi Yang, Ren Wang, Xiao-Xing Li, Yang Yang, Hui-Yun Wang, X. F. Steven Zheng. Rab1A and Rab1B promote esophageal squamous cell carcinoma through activating mTORC1 signaling and inhibiting autophagy. [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 1029.