β-catenin nuclear translocation induced by HIF-1α overexpression leads to the radioresistance of prostate cancer
dc.contributor.author | Luo, YONG | |
dc.contributor.author | Li, MINGCHUAN | |
dc.contributor.author | Zuo, XUEMEI | |
dc.contributor.author | BASOURAKOS, SPYRIDON P. | |
dc.contributor.author | Zhang, JIAO | |
dc.contributor.author | Zhao, JIAHUI | |
dc.contributor.author | Han, Yili | |
dc.contributor.author | Lin, YUNHUA | |
dc.contributor.author | Wang, YONGXING | |
dc.contributor.author | Jiang, YONGGUANG | |
dc.contributor.author | Lan, Ling | |
dc.date.accessioned | 2020-04-03T18:36:53Z | |
dc.date.available | 2020-04-03T18:36:53Z | |
dc.date.issued | 2018-03-16 | |
dc.description.abstract | Hypoxia-inducible factor-1α (HIF-1α) is known to play crucial roles in tumor radioresistance; however, the molecular mechanisms responsible for the promotion of tumor radioresistance by HIF-1α remain unclear. β-catenin is known to be involved in the metastatic potential of prostate cancer (PCa). In this study, to investigate the role of HIF-1α and β-catenin in the radioresistance of PCa, two PCa cell lines, LNCaP and C4-2B, were grouped as follows: Negative control (no treatment), HIF-1α overexpression group (transfected with HIF-1α overexpression plasmid) and β-catenin silenced group (transfected with HIF-1α plasmids and β-catenin-shRNA). Cell proliferation, cell cycle, cell invasion and radiosensitivity were examined under normal or hypoxic conditions. In addition, radiosensitivity was examined in two mouse PCa models (the LNCaP orthotopic BALB/c-nu mice model and the C4-2B subcutaneous SCID mice model). Our results revealed that in both the LNCaP and C4-2B cells, transfection with HIF-1α overexpression plasmid led to an enhanced β-catenin nuclear translocation, while β-catenin silencing inhibited β-catenin nuclear translocation. The enhanced β-catenin nuclear translocation induced by HIF-1α overexpression resulted in an enhanced cell proliferation and cell invasion, an altered cell cycle distribution, decreased apoptosis, and improved non-homologous end joining (NHEJ) repair under normal and irradiation conditions. Similar results were observed in the animal models. HIF-1α overexpression enhanced β-catenin nuclear translocation, which led to the activation of the β-catenin/NHEJ signaling pathway and increased cell proliferation, cell invasion and DNA repair. These results thus suggest that HIF-1α overexpression promotes the radioresistance of PCa cells. | en_US |
dc.identifier.doi | 10.3892/ijo.2018.4368 | |
dc.identifier.uri | http://hdl.handle.net/10342/7942 | |
dc.title | β-catenin nuclear translocation induced by HIF-1α overexpression leads to the radioresistance of prostate cancer | en_US |
dc.type | Article | en_US |
ecu.journal.issue | 6 | en_US |
ecu.journal.name | International Journal of Oncology | en_US |
ecu.journal.pages | 1827-1840 | en_US |
ecu.journal.volume | 52 | en_US |
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