TNF-α inducible protein (TNFAIP8) is an antiapoptotic protein with roles in tumor cell growth and survival. Mechanisms of cell survival by TNFAIP8 remains elusive. In the current study, we investigated the role and molecular mechanism related to TNFAIP8 in the modulation of cell/cycle, autophagy and drug resistance/cell survival in prostate cancer cells. Microarray data from PC3 prostate cancer cells ectopically expressing TNFAIP8 demonstrated modulation of cell cycle related genes such as CDKs, CDCs and PCNA. Immunoblotting data from overexpression of TNFAIP8 in PC3 cells shows upregulation of cell cycle proteins cyclin A, cyclin B1, Myt1 and Chk1. However, no change in cell cycle was found. Phosphorylation of Histone-S10, CDC2-Tyr15 and Wee1-S642] was also observed. Autophagy plays an important role in tumor cell survival. We evaluated the effects of TNFAIP8 in modulating autophagy. Overexpression of TNFAIP8 leads to induction of autophagy. TNFAIP8 positively modulates the expression/stabilization of autophagy markers and effectors such as LC3β I/II, Beclin1, 4EBP1, oncogene p62 and SIRT1. Knockdown of TNFAIP8 inhibits autophagy induced by nutrient starvation in PC3 prostate and MCF7 breast cancer cells. We also evaluated cell growth and survival in PC3 cells. We demonstrate that TNFAIP8 promotes cell growth and proliferation in PC3, LNCaP and C4-2 prostate cancer cells. Furthermore, we have found that TNFAIP8 increase resistance against anticancer drugs docetaxel and doxorubicin. These data collectively suggest that by the creation of cellular autophagy events TNFAIP8 promotes cell survival and drug resistance in prostate cancer cells.

Citation Format: Suresh Niture, Malathi Ramalinga, Habib Kedir, Deepak Kumar. TNFAIP8 promotes prostate cancer cell survival by modulating autophagy [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 2342. doi:10.1158/1538-7445.AM2017-2342