title: IFNg-induced Irgm1 promotes tumorigenesis of melanoma via dual regulation of apoptosis and Bif-1-dependent autophagy.
abstract: Interferon gamma (IFNg) has been known as the regulator for both tumor immune surveillance and tumorgenesis. However, mechanisms underlying the resistance of tumor cell to IFNg have yet been fully understood. In the current study, we showed that immunity-related GTPase family member 1 (mouse: Irgm1; human: IRGM) is essential for IFNg-mediated regulation of tumor cell growth in melanoma. IRGM/Irgm1 was highly expressed in human and mouse melanoma. IFNg and starvation synergistically induced Irgm1 expression in melanoma B16 cells. In vivo, injection of Irgm1-siRNA-treated cells significantly reduced the number of tumor nodules and prolonged the mice survival. In vitro, knockdown endogenous or IFNg-induced Irgm1 significantly decreases the proliferation and increases apoptosis of B16 cells. In addition, suppressing Irgm1 decreased the IFNg/starvation-induced autophagy, while overexpressing Irgm1 significantly increased autophagy and rescued starvation-challenged cells. Moreover, IFNg and starvation-induced the co-localization of Irgm1 with Bax-interacting factor 1 (Bif-1). Knockdown of Bif-1 decreased Irgm1-mediated tumor cell autophagy. Taken together, these data reveal an Irgm1-dependent mechanism that promotes the tumorigenesis of melanoma via dual regulation of apoptosis and Bif-1-dependent autophagy.
authors.affiliation: Department of Immunology, Heilongjiang Provincial Key Laboratory for Infection and Immunity, Harbin Medical University, Harbin, China.|Department of Neurology, The Affiliated Sanming First Hospital of Fujian Medical University, Sanming, Fujian, China.
authors.forename: H
authors.initials: H
authors.lastname: Dong
authors.affiliation: Department of Immunology, Heilongjiang Provincial Key Laboratory for Infection and Immunity, Harbin Medical University, Harbin, China.
authors.forename: L
authors.initials: L
authors.lastname: Tian
authors.affiliation: Neuroinflammation Unit, Montreal Neurological Institute, McGill University, Montreal, Quebec, Canada.
authors.forename: R
authors.initials: R
authors.lastname: Li
authors.affiliation: Department of Immunology, Heilongjiang Provincial Key Laboratory for Infection and Immunity, Harbin Medical University, Harbin, China.
authors.forename: C
authors.initials: C
authors.lastname: Pei
authors.affiliation: Department of Immunology, Heilongjiang Provincial Key Laboratory for Infection and Immunity, Harbin Medical University, Harbin, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Fu
authors.affiliation: Department of Immunology, Heilongjiang Provincial Key Laboratory for Infection and Immunity, Harbin Medical University, Harbin, China.
authors.forename: X
authors.initials: X
authors.lastname: Dong
authors.affiliation: Department of Immunology, Heilongjiang Provincial Key Laboratory for Infection and Immunity, Harbin Medical University, Harbin, China.
authors.forename: F
authors.initials: F
authors.lastname: Xia
authors.affiliation: Department of Immunology, Heilongjiang Provincial Key Laboratory for Infection and Immunity, Harbin Medical University, Harbin, China.
authors.forename: C
authors.initials: C
authors.lastname: Wang
authors.affiliation: Department of Immunology, Heilongjiang Provincial Key Laboratory for Infection and Immunity, Harbin Medical University, Harbin, China.
authors.forename: W
authors.initials: W
authors.lastname: Li
authors.affiliation: Department of Immunology, Heilongjiang Provincial Key Laboratory for Infection and Immunity, Harbin Medical University, Harbin, China.
authors.forename: X
authors.initials: X
authors.lastname: Guo
authors.affiliation: Department of Immunology, Heilongjiang Provincial Key Laboratory for Infection and Immunity, Harbin Medical University, Harbin, China.
authors.forename: C
authors.initials: C
authors.lastname: Gu
authors.affiliation: Department of Immunology, Heilongjiang Provincial Key Laboratory for Infection and Immunity, Harbin Medical University, Harbin, China.
authors.forename: B
authors.initials: B
authors.lastname: Li
authors.affiliation: Department of Hematology, The Affiliated Tumor Hospital of Harbin Medical University, Harbin, China.
authors.forename: A
authors.initials: A
authors.lastname: Liu
authors.affiliation: Department of Immunology, Heilongjiang Provincial Key Laboratory for Infection and Immunity, Harbin Medical University, Harbin, China.
authors.forename: H
authors.initials: H
authors.lastname: Ren
authors.affiliation: Department of Neurology, The Affiliated Sanming First Hospital of Fujian Medical University, Sanming, Fujian, China.
authors.forename: C
authors.initials: C
authors.lastname: Wang
authors.affiliation: Department of Immunology, Heilongjiang Provincial Key Laboratory for Infection and Immunity, Harbin Medical University, Harbin, China.
authors.forename: H
authors.initials: H
authors.lastname: Xu
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000502:physiology*; D000818:Animals; D017209:Apoptosis; D001343:Autophagy; D045744:Cell Line, Tumor; D002470:Cell Survival; D019204:GTP-Binding Proteins / Q000502:physiology*; D006801:Humans; D007371:Interferon-gamma / Q000502:physiology*; D008545:Melanoma / Q000209:etiology* / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C096000:Ifi1 protein, mouse; C429293:SH3GLB1 protein, human; C486100:Sh3glb1 protein, mouse; D007371:Interferon-gamma; D019204:GTP-Binding Proteins; C513539:IRGM protein, human