title: Type I interferons induce autophagy in certain human cancer cell lines.
abstract: Autophagy is an evolutionarily conserved cellular recycling mechanism that occurs at a basal level in all cells. It can be further induced by various stimuli including starvation, hypoxia, and treatment with cytokines such as IFNG/IFNγ and TGFB/TGFβ. Type I IFNs are proteins that induce an antiviral state in cells. They also have antiproliferative, proapoptotic and immunomodulatory activities. We investigated whether type I IFN can also induce autophagy in multiple human cell lines. We found that treatment with IFNA2c/IFNα2c and IFNB/IFNβ induces autophagy by 24 h in Daudi B cells, as indicated by an increase of autophagy markers MAP1LC3-II, ATG12-ATG5 complexes, and a decrease of SQSTM1 expression. An increase of MAP1LC3-II was also detected 48 h post-IFNA2c treatment in HeLa S3, MDA-MB-231, T98G and A549 cell lines. The presence of autophagosomes in selected cell lines exposed to type I IFN was confirmed by electron microscopy analysis. Increased expression of autophagy markers correlated with inhibition of MTORC1 in Daudi cells, as well as inhibition of cancer cell proliferation and changes in cell cycle progression. Concomitant blockade of either MTOR or PI3K-AKT signaling in Daudi and T98G cells treated with IFNA2c increased the level of MAP1LC3-II, indicating that the PI3K-AKT-MTORC1 signaling pathway may modulate IFN-induced autophagy in these cells. Taken together, our findings demonstrated a novel function of type I IFN as an inducer of autophagy in multiple cell lines.
authors: National Institutes of Health, National Institute of Allergy and Infectious Disease, Cytokine Biology Section, Bethesda, MD, USA.
authors: Hana
authors: H
authors: Schmeisser
authors: Samuel B
authors: SB
authors: Fey
authors: Julie
authors: J
authors: Horowitz
authors: Elizabeth R
authors: ER
authors: Fischer
authors: Corey A
authors: CA
authors: Balinsky
authors: Kotaro
authors: K
authors: Miyake
authors: Joseph
authors: J
authors: Bekisz
authors: Andrew L
authors: AL
authors: Snow
authors: Kathryn C
authors: KC
authors: Zoon
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D001343:Autophagy / Q000187:drug effects*; D000071187:Autophagy-Related Protein 5; D015415:Biomarkers / Q000378:metabolism; D002448:Cell Adhesion / Q000187:drug effects; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D006801:Humans; D007370:Interferon Type I / Q000494:pharmacology*; D000076222:Mechanistic Target of Rapamycin Complex 1; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D046912:Multiprotein Complexes / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism; D038601:Ribosomal Protein S6 / Q000378:metabolism; D000071456:Sequestosome-1 Protein; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism
chemical_list: C502778:ATG5 protein, human; D048868:Adaptor Proteins, Signal Transducing; D000071187:Autophagy-Related Protein 5; D015415:Biomarkers; D007370:Interferon Type I; C477012:MAP1LC3A protein, human; D008869:Microtubule-Associated Proteins; D046912:Multiprotein Complexes; D034741:RNA, Small Interfering; D038601:Ribosomal Protein S6; C099718:SQSTM1 protein, human; D000071456:Sequestosome-1 Protein; C546842:MTOR protein, human; D000076222:Mechanistic Target of Rapamycin Complex 1; D051057:Proto-Oncogene Proteins c-akt; D058570:TOR Serine-Threonine Kinases; D020928:Mitogen-Activated Protein Kinases
keywords: AKT; MTORC1; PI3K; autophagy; human cancer cells; signal transduction; type I interferon