title: IRGM1 enhances B16 melanoma cell metastasis through PI3K-Rac1 mediated epithelial mesenchymal transition.
abstract: Melanoma is one of the most aggressive skin cancers and is well known for its high metastatic rate. Studies have shown that epithelial mesenchymal transition (EMT) is essential for melanoma cell metastasis. However, the molecular mechanisms underlying EMT are still not fully understood. We have shown that IRGM1, a member of immunity-related GTPase family that regulates immune cell motility, is highly expressed by melanoma cells. The current study aimed to explore whether and how IRGM1 may regulate melanoma cell metastasis. To test this, we modified IRGM1 expression in B16 melanoma cells. We found that over-expression of IRGM1 substantially enhanced pulmonary metastasis in vivo. In keeping with that, knocking-in IRGM1 strongly enhanced while knocking-down IRGM1 impaired B16 cell migration and invasion ability in vitro. Interestingly, we observed that IRGM1 enhanced F-actin polymerization and triggers epithelial mesenchymal transition (EMT) through a mechanism involved in PIK3CA mediated Rac1 activation. Together, these data reveals a novel molecular mechanism that involved in melanoma metastasis.
authors.affiliation: Department of Immunology, Heilongjiang Provincial Key Laboratory for Infection and Immunity, Harbin Medical University, Harbin 150081, China.
authors.forename: Linlu
authors.initials: L
authors.lastname: Tian
authors.affiliation: Department of Neurosurgery, The Affiliated First Hospital of Harbin Medical University, Harbin 150001, China.
authors.forename: Lixian
authors.initials: L
authors.lastname: Li
authors.affiliation: Department of Immunology, Heilongjiang Provincial Key Laboratory for Infection and Immunity, Harbin Medical University, Harbin 150081, China.
authors.forename: Wenjing
authors.initials: W
authors.lastname: Xing
authors.affiliation: Neuroimmunology Unit, Montreal Neurological Institute, McGill University, Montreal H3A2B4, Canada.
authors.forename: Rui
authors.initials: R
authors.lastname: Li
authors.affiliation: Department of Immunology, Heilongjiang Provincial Key Laboratory for Infection and Immunity, Harbin Medical University, Harbin 150081, China.
authors.forename: Chunying
authors.initials: C
authors.lastname: Pei
authors.affiliation: Department of Immunology, Heilongjiang Provincial Key Laboratory for Infection and Immunity, Harbin Medical University, Harbin 150081, China.
authors.forename: Xiao
authors.initials: X
authors.lastname: Dong
authors.affiliation: Department of Immunology, Heilongjiang Provincial Key Laboratory for Infection and Immunity, Harbin Medical University, Harbin 150081, China.
authors.forename: Yanran
authors.initials: Y
authors.lastname: Fu
authors.affiliation: Department of Immunology, Heilongjiang Provincial Key Laboratory for Infection and Immunity, Harbin Medical University, Harbin 150081, China.
authors.forename: Changcong
authors.initials: C
authors.lastname: Gu
authors.affiliation: Department of Immunology, Heilongjiang Provincial Key Laboratory for Infection and Immunity, Harbin Medical University, Harbin 150081, China.
authors.forename: Xize
authors.initials: X
authors.lastname: Guo
authors.affiliation: Department of Neurosurgery, The Affiliated First Hospital of Harbin Medical University, Harbin 150001, China.
authors.forename: Yulong
authors.initials: Y
authors.lastname: Jia
authors.affiliation: Department of Neurobiology, Harbin Medical University, Harbin 150081, China.
authors.forename: Guangyou
authors.initials: G
authors.lastname: Wang
authors.affiliation: Department of Neurobiology, Harbin Medical University, Harbin 150081, China.
authors.forename: Jinghua
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Immunology, Heilongjiang Provincial Key Laboratory for Infection and Immunity, Harbin Medical University, Harbin 150081, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Li
authors.affiliation: Department of Immunology, Heilongjiang Provincial Key Laboratory for Infection and Immunity, Harbin Medical University, Harbin 150081, China.
authors.forename: Huan
authors.initials: H
authors.lastname: Ren
authors.affiliation: Department of Immunology, Heilongjiang Provincial Key Laboratory for Infection and Immunity, Harbin Medical University, Harbin 150081, China.
authors.forename: Hongwei
authors.initials: H
authors.lastname: Xu
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D058750:Epithelial-Mesenchymal Transition; D019204:GTP-Binding Proteins / Q000378:metabolism*; D008175:Lung Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000556:secondary*; D008545:Melanoma / Q000378:metabolism* / Q000473:pathology / Q000556:secondary*; D051379:Mice; D008810:Mice, Inbred C57BL; D009361:Neoplasm Invasiveness; D009479:Neuropeptides / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D015398:Signal Transduction; D020830:rac1 GTP-Binding Protein / Q000378:metabolism
chemical_list: C096000:Ifi1 protein, mouse; D009479:Neuropeptides; C484602:Rac1 protein, mouse; D019869:Phosphatidylinositol 3-Kinases; D019204:GTP-Binding Proteins; D020830:rac1 GTP-Binding Protein