PI3K/AKT/mTORC1-signaling pathway plays a role in induction of autophagy by type I interferons

Wednesday, November 06, 2013 — Poster Session I
4:00 p.m. – 6:00 p.m.	FAES Academic Center (Upper-Level Terrace)	NIAID	CANCER-16

Authors

H. Schmeisser
S.B. Fey
J. Horowitz
E.R. Fischer
C.A. Balinsky
K. Miyake
J. Bekisz
A.L. Snow
K.C. Zoon

Abstract

Autophagy is a stress-induced cellular recycling mechanism that occurs at a basal level in all eukaryotic cells. Type I interferons are cytokines that have the ability to induce antiviral, antiproliferative and immunomodulatory activities in cells. Recently, we found that treatment with IFN-alpha2c and IFN-beta induces autophagy in Daudi B cells, starting at 24 h as indicated by an increase of autophagy markers LC3-II, Atg5-Atg12 complexes, and a decrease of p62. Higher levels of LC3-II were also detected 48 h post IFN-alpha2c treatment in HeLa S3, MDA-MB-231, T98G and A549 cell lines. The increase in expression of autophagy markers correlated with inhibition of mTORC1 activity in Daudi cells. Treatment of Daudi and T98G cells with IFN-alpha2c in combination with either rapamycin (mTORC1 inhibitor) or LY294002 (PI3K inhibitor) increased the level of LC3-II, indicating that PI3K/AKT/mTORC1 signaling pathway may affect IFN-induced autophagy in Daudi and T98G cells. The role of mTOR and factors upstream of mTOR in Type I IFN-induced autophagy was confirmed by siRNA knockdown experiments. The presence of autophagosomes was shown using transmission electron microscopy. In conclusion, our findings demonstrate a novel function of Type I IFN as inducer of autophagy in a variety of cancer cell lines.