Induction of autophagy by Type I interferon in human cancer cells (P6217)

Abstract

Abstract Type I IFNs (interferons) are cytokines that induce an antiviral state in cells and have antiproliferative, pro-apoptotic, and immunomodulatory activities. Autophagy is a basic cellular mechanism that involves degradation of cellular components via lysosomes. While induction of autophagy is well documented for Type II IFN, induction of autophagy by Type I IFN has not been previously reported. We determined that Type I IFN can induce autophagy in multiple human cancer cell lines. IFN-α2c and IFN-β induces autophagy in Daudi B cells, as indicated by an increase in autophagy markers LC3-II, Atg5-Atg12 complexes, and a decrease in p62. An increase in LC3-II was also detected post IFN-α2c treatment in HeLa S3, MDA-MB-231, T98G and A549 cell lines. The presence of autophagosomes in selected cell lines was confirmed by electron microscopy analysis. An increase in autophagy markers correlated with inhibition of mTORC1 activity and cell proliferation as well as changes in the cell cycle progression in Daudi cells. Treatment of Daudi and T98G cells with IFN-α2c and rapamycin (mTOR inhibitor), or LY294002 (PI3K inhibitor) increased the level of LC3-II, indicating that the PI3K/Akt/mTORC1 signaling pathway may affect IFN-induced autophagy in Daudi and T98G cells. The role of mTOR in Type I IFN-induced autophagy was confirmed by siRNA silencing experiments. Taken together, our findings demonstrate a novel function for Type I IFN as inducer of autophagy in multiple cancer cell lines.