Tang Jianming, Shi Huijuan, Li Hui, Zhen Tiantian, Dong Yu, Zhang Fenfen, Yang Yang, Han Anjia
Department of Pathology, the First Affiliated Hospital, Sun Yat-Sen University, 58, Zhongshan Road II, Guangzhou, 510080, China.
Tumour Biol. 2016 Aug;37(8):10287-301. doi: 10.1007/s13277-016-4905-5. Epub 2016 Feb 2.
To clarify the clinicopathological and biological role of hepatoma-derived growth factor (HDGF) and β-catenin in synovial sarcoma. Our results showed that histological type and HDGF/β-catenin expression were the two important independent prognostic factors for overall survival in synovial sarcoma patients. HDGF knockdown dramatically inhibited cellular proliferation, colony formation, and migration but induced G1 phase arrest and apoptosis in SW982 cells. Recombinant HDGF enhanced synovial sarcoma cell growth and partially retrieved the cell growth suppression in SW982 cells upon HDGF knockdown. HDGF knockdown dramatically suppressed β-catenin and its downstream gene expression in SW982 cells. Intriguingly, β-catenin knockdown dramatically suppressed HDGF expression in SW982 cells. A direct interaction of HDGF and β-catenin was found in SW982 cells. Three HDGF-binding elements in β-catenin promoter were found and specific for transcriptional activation of β-catenin in SW982 cells. In conclusion, our findings first indicate that the interaction of HDGF and β-catenin may play a crucial role in tumorigenesis of synovial sarcoma.
为阐明肝癌衍生生长因子(HDGF)和β-连环蛋白在滑膜肉瘤中的临床病理及生物学作用。我们的结果显示,组织学类型和HDGF/β-连环蛋白表达是滑膜肉瘤患者总生存的两个重要独立预后因素。HDGF基因敲低显著抑制SW982细胞的细胞增殖、集落形成和迁移,但诱导其G1期阻滞和凋亡。重组HDGF增强滑膜肉瘤细胞生长,并部分恢复HDGF基因敲低后SW982细胞的生长抑制。HDGF基因敲低显著抑制SW982细胞中β-连环蛋白及其下游基因表达。有趣的是,β-连环蛋白基因敲低显著抑制SW982细胞中HDGF表达。在SW982细胞中发现HDGF与β-连环蛋白存在直接相互作用。在β-连环蛋白启动子中发现三个HDGF结合元件,它们对SW982细胞中β-连环蛋白的转录激活具有特异性。总之,我们的研究结果首次表明,HDGF与β-连环蛋白的相互作用可能在滑膜肉瘤的肿瘤发生中起关键作用。