Abstract B120: TIPE2 regulates apoptosis and autophagy to inhibit tumorigenesis in colon cancer

Abstract

Abstract TIPE2 is an important immune negative regulator which regulates innate immunity and adaptive immunity to maintain immune homeostasis. Abnormal expression of TIPE2 is related to many acute and chronic inflammatory diseases, as well as the tumorigenesis. Here, we identified that overexpression of TIPE2 in colon cancer cell line inhibited cell growth. Recombinant adenovirus-expression TIPE2 effectively inhibited the proliferation of several kinds of cancer cell. Using protein biochip ananlysis, we found that in the TIPE2-overexpressing colon cancer cell, the expression levels of phosphorylated p38-MAPK/JNK, pro-apoptotic survivin were downregulated. These results suggest TIPE2 regulates tumor cell growth though p38-MAPK/JNK pathway. Western blot analysis showed that the proliferation level of AKT and the expression level of Bad were also changed in the TIPE2-overexpressing colon cancer cell, suggesting that TIPE2 may inhibit tumor cell proliferation through inducing cell death. Using flow cytometry analysis, we found that the overexpression of TIPE2 could promote apoptosis of tumor cell while knockdown of TIPE2 expression by shRNA could inhibit apoptosis. Previous studies have demonstrated that p38-MAPK/JNK and Akt pathway play important roles in autophagy. In this study, with the accumulation of LC3-II by stimulating TIPE2, tumor autophagy was increased in vitro. Thus, the function of TIPE2 in the inhibition of tumorigenesis may have broad implications in cancer gene therapy. Citation Format: Jun Li, Xiaoli Xia. TIPE2 regulates apoptosis and autophagy to inhibit tumorigenesis in colon cancer [abstract]. In: Proceedings of the Fourth CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference: Translating Science into Survival; Sept 30-Oct 3, 2018; New York, NY. Philadelphia (PA): AACR; Cancer Immunol Res 2019;7(2 Suppl):Abstract nr B120.