title: A regulatory feedback loop between HIF-1α and PIM2 in HepG2 cells.
abstract: To survive under hypoxic conditions, cancer cells remodel glucose metabolism to support tumor progression. HIF transcription factor is essential for cellular response to hypoxia. The underlying mechanism how HIF is constitutively activated in cancer cells remains elusive. In the present study, we characterized a regulatory feedback loop between HIF-1α and PIM2 in HepG2 cells. Serine/threonine kinase proto-oncogene PIM2 level was induced upon hypoxia in a HIF-1α-mediated manner in cancer cells. HIF-1α induced PIM2 expression via binding to the hypoxia-responsive elements (HREs) of the PIM2 promoter. In turn, PIM2 interacted with HIF-1α, especially a transactivation domain of HIF-1α. PIM2 as a co-factor but not an upstream kinase of HIF-1α, enhanced HIF-1α effect in response to hypoxia. The positive feedback loop between PIM2 and HIF-1α was correlated with glucose metabolism as well as cell survival in HepG2 cells. Such a regulatory mode may be important for the adaptive responses of cancer cells in antagonizing hypoxia during cancer progression.
authors: School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, China.
authors: Zhenhai
authors: Z
authors: Yu
authors: Department of Nuclear Medicine, Ren ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
authors: Xiaoping
authors: X
authors: Zhao
authors: State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou, China.
authors: Yingying
authors: Y
authors: Ge
authors: Department of Nuclear Medicine, Ren ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
authors: Teng
authors: T
authors: Zhang
authors: Institute of Health Sciences, Shanghai Jiao Tong University School of Medicine (SJTUSM) & Shanghai Institutes for Biological Sciences (SIBS), Chinese Academy of Sciences (CAS), Shanghai, China.
authors: Liangqian
authors: L
authors: Huang
authors: Department of Nuclear Medicine, Ren ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
authors: Xiang
authors: X
authors: Zhou
authors: Department of Nuclear Medicine, Ren ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
authors: Lei
authors: L
authors: Xie
authors: Department of Nuclear Medicine, Ren ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
authors: Jianjun
authors: J
authors: Liu
authors: Department of Nuclear Medicine, Ren ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China ; School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, China ; Institute of Health Sciences, Shanghai Jiao Tong University School of Medicine (SJTUSM) & Shanghai Institutes for Biological Sciences (SIBS), Chinese Academy of Sciences (CAS), Shanghai, China.
authors: Gang
authors: G
authors: Huang
mesh_terms: D015687:Cell Hypoxia; D015972:Gene Expression Regulation, Neoplastic; D005947:Glucose / Q000378:metabolism; D056945:Hep G2 Cells; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism*; D009369:Neoplasms / Q000235:genetics / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D051795:Hypoxia-Inducible Factor 1, alpha Subunit; C000715470:MAS1 protein, human; C490587:PIM2 protein, human; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins; D017346:Protein Serine-Threonine Kinases; D005947:Glucose