title: Hypoxia promotes epithelial--mesenchymal transition of hepatocellular carcinoma cells via inducing GLIPR-2 expression.
abstract: Glioma pathogenesis related-2 (GLIPR-2) belongs to pathogenesis related-1 (PR-1) family whose function remains unknown. In our previous studies, GLIPR-2 was found to be a novel potent stimulator of epithelial-to-mesenchymal transition (EMT) in renal fibrosis which has been classified as type 2 EMT. However, whether GLIPR-2 could induce type 3 EMT in carcinogenesis needs further investigation. In this study, we showed that GLIPR-2 was expressed in hepatocellular carcinoma (HCC) tissues, hypoxia could upregulate the expression of GLIPR-2 in HepG2 and PLC/PRF/5 cells in vitro, overexpression of this protein promoted migration and invasion via EMT, knockdown of GLIPR-2 attenuated migration and invasion of HepG2 and PLC/PRF/5 cells in hypoxia. Moreover, extracellular signal-regulated kinases 1 and 2 (ERK1/2) are positively regulated by GLIPR-2. Taken together, we provide evidence for a hypoxia/GLIPR-2/EMT/migration and invasion axis in HCC cells and it provides novel insights into the mechanism of migration and invasion of hepatocellular carcinoma cells in hypoxia condition.
authors.affiliation: Department of Clinical Laboratory, Xin Qiao Hospital, Third Military Medical University, Chong Qing, People's Republic of China.
authors.forename: Shao-guang
authors.initials: SG
authors.lastname: Huang
authors.forename: Le-le
authors.initials: LL
authors.lastname: Zhang
authors.forename: Qin
authors.initials: Q
authors.lastname: Niu
authors.forename: Gui-ming
authors.initials: GM
authors.lastname: Xiang
authors.forename: Lin-lin
authors.initials: LL
authors.lastname: Liu
authors.forename: Dong-neng
authors.initials: DN
authors.lastname: Jiang
authors.forename: Fei
authors.initials: F
authors.lastname: Liu
authors.forename: Yi
authors.initials: Y
authors.lastname: Li
authors.forename: Xiaoyun
authors.initials: X
authors.lastname: Pu
mesh_terms: D006528:Carcinoma, Hepatocellular / Q000150:complications / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D002465:Cell Movement; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic; D056945:Hep G2 Cells; D006801:Humans; D000860:Hypoxia / Q000150:complications / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D008113:Liver Neoplasms / Q000150:complications / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D008565:Membrane Proteins / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D019950:Mitogen-Activated Protein Kinase 1 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction
chemical_list: C458481:GLIPR2 protein, human; D008565:Membrane Proteins; D034741:RNA, Small Interfering; C535150:MAPK1 protein, human; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3