title: New function of TSGA10 gene in angiogenesis and tumor metastasis: a response to a challengeable paradox.
abstract: Several studies have shown that testis-specific gene antigen (TSGA10) could be considered as a cancer testis antigen (CTA), except for one study which has identified it as a tumor suppressor gene. In order to exert its function, TSGA10 interacts closely with hypoxia inducible factor (HIF-1α) and since this interaction is still not completely defined, the exact role of TSGA10 in angiogenesis and invasion is also under question. The current study was conducted to investigate the function of TSGA10 gene and evaluate its potential effects on tumor angiogenesis and invasion. To do so, TSGA10 vector was designed for a stable transfection in HeLa cells, and then clonal selection was applied. The efficiency of transfection and the role of TSGA10 in abovementioned targets were evaluated by real-time PCR, western blot, zymography and ELISA tests in both normoxia and hypoxia. Invasion, migration and angiogenesis were assessed. Three-dimensional model of TSGA10 protein was accurately built in which TSGA10 docked to 2 domains of HIF-1α. Increased expression of TSGA10 correlated with decreased HIF-1α transcriptional activity and inhibited angiogenesis and HeLa cells invasion in normoxia as well as hypoxia. Docking analysis indicated that binding affinity of TSGA10 with TAD-C (CBP) domain of HIF-1α would be stronger than that with PAS-B domain. Our findings showed that overexpression of TSGA10 would induce disruption of HIF-1α axis and exert potent inhibitory effects on tumor angiogenesis and metastasis. Therefore, TSGA10 could be considered as a potent therapeutic candidate, prognostic factor and a cancer management tool.
authors.affiliation: Department of Molecular Medicine, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran and Medical Biology Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran.
authors.forename: Kamran
authors.initials: K
authors.lastname: Mansouri
authors.affiliation: Medical Biology Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran.
authors.forename: Ali
authors.initials: A
authors.lastname: Mostafie
authors.affiliation: Department of Molecular Medicine, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran and Medical Biology Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran.
authors.forename: Davood
authors.initials: D
authors.lastname: Rezazadeh
authors.affiliation: Medical Biology Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran.
authors.forename: Mohsen
authors.initials: M
authors.lastname: Shahlaei
authors.affiliation: Department of Molecular Medicine, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran and modaresi@tums.ac.ir.
authors.forename: Mohammad Hossein
authors.initials: MH
authors.lastname: Modarressi
mesh_terms: D001665:Binding Sites; D003598:Cytoskeletal Proteins; D005260:Female; D006367:HeLa Cells; D006801:Humans; D000860:Hypoxia; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism*; D062105:Molecular Docking Simulation; D009362:Neoplasm Metastasis; D009389:Neovascularization, Pathologic / Q000378:metabolism*; D011506:Proteins / Q000378:metabolism*
chemical_list: D003598:Cytoskeletal Proteins; C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D011506:Proteins; C429756:TSGA10 protein, human