title: Nuclear EGFRvIII resists hypoxic microenvironment induced apoptosis via recruiting ERK1/2 nuclear translocation.
abstract: Glioblastoma (GBM) is the most aggressive type of primary brain tumor. Its interaction with the tumor microenvironment promotes tumor progression. Furthermore, GBM bearing expression of EGFRvIII displays more adaptation to tumor microenvironment related stress. But the mechanisms were poorly understood. Here, we presented evidence that in the human U87MG glioblastoma tumor model, EGFRvIII overexpression led aberrant kinase activation and nuclear translocation of EGFRvIII/ERK1/2 under hypoxia, which induced growth advantage by resisting apoptosis. Additionally, EGFRvIII defective in nuclear entry impaired this capacity in hypoxia adaptation, and partially interrupted ERK1/2 nuclear translocation. Pharmacology or genetic interference ERK1/2 decreased hypoxia resistance triggered by EGFRvIII expression, but not EGFRvIII nuclear translocation. In summary, this study identified a novel role for EGFRvIII in hypoxia tolerance, supporting an important link between hypoxia and subcellular localization alterations of the receptor.
authors.affiliation: Dept. of Immunology, Harbin Medical University, Harbin 150081, China; Key Lab Infection & Immunity, Heilongjiang Province, Harbin 150081, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Xie
authors.affiliation: Dept. of Immunology, Harbin Medical University, Harbin 150081, China; Key Lab Infection & Immunity, Heilongjiang Province, Harbin 150081, China.
authors.forename: Jinfeng
authors.initials: J
authors.lastname: Yang
authors.affiliation: Dept. of Immunology, Harbin Medical University, Harbin 150081, China; Key Lab Infection & Immunity, Heilongjiang Province, Harbin 150081, China.
authors.forename: Wenjing
authors.initials: W
authors.lastname: Xing
authors.affiliation: Dept. of Immunology, Harbin Medical University, Harbin 150081, China; Key Lab Infection & Immunity, Heilongjiang Province, Harbin 150081, China.
authors.forename: Yucui
authors.initials: Y
authors.lastname: Dong
authors.affiliation: Dept. of Immunology, Harbin Medical University, Harbin 150081, China; Key Lab Infection & Immunity, Heilongjiang Province, Harbin 150081, China. Electronic address: renhuan@ems.hrbmu.edu.cn.
authors.forename: Huan
authors.initials: H
authors.lastname: Ren
mesh_terms: D021581:Active Transport, Cell Nucleus / Q000502:physiology; D017209:Apoptosis; D015687:Cell Hypoxia / Q000502:physiology; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000378:metabolism*; D049109:Cell Proliferation; D060833:Cellular Microenvironment; D066246:ErbB Receptors / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000502:physiology; D005909:Glioblastoma / Q000378:metabolism* / Q000473:pathology*; D006801:Humans; D020935:MAP Kinase Signaling System / Q000502:physiology; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism*; D010100:Oxygen / Q000378:metabolism
chemical_list: C410723:epidermal growth factor receptor VIII; D066246:ErbB Receptors; C535150:MAPK1 protein, human; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D010100:Oxygen
keywords: EGFRvIII; ERK1/2; Glioblastoma; Hypoxia; Nuclear translocation