Jiang L, Zhou J, Zhong D, Zhou Y, Zhang W, Wu W, Zhao Z, Wang W, Xu W, He L, Ma Y, Hu Y, Zhang W, Li J
Key Laboratory of Protein Modification and Degradation, School of Basic Medical Sciences; Affiliated Cancer Hospital and Institute of Guangzhou Medical University, Guangzhou Medical University, Guangzhou, China.
Guangdong Province Key Laboratory of Brain Function and Disease, Department of Biochemistry, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, China.
Oncogenesis. 2017 Mar 13;6(3):e301. doi: 10.1038/oncsis.2017.8.
Overexpression of structural maintenance of chromosomes 4 (SMC4) has been reported to be involved in tumor cell growth, migration and invasion, and to be correlated with poor prognosis of cancer patient. However, its clinical significance and biological role in glioma remain unknown. Herein, we found that SMC4 expression at both mRNA and protein level was markedly increased in glioma cells and clinical tissues and that it correlated with poor prognosis. SMC4 overexpression markedly promoted the glioma cell proliferation rate and migration and invasive capability in vitro and in vivo, whereas SMC4 downregulation reduced it. Moreover, the transforming growth factor β (TGFβ)/Smad signaling pathway, which was activated in SMC4-transduced glioma cells and inhibited in SMC4-silenced glioma cells, contributed to SMC4-mediated glioma cell aggressiveness. Our results provide new insight into the oncofunction of SMC4 and the mechanism by which the TGFβ/Smad pathway is hyperactivated in gliomas, indicating that SMC4 is a valuable prognostic factor and a potential therapeutic target in gliomas.
据报道，染色体结构维持蛋白4（SMC4）的过表达与肿瘤细胞的生长、迁移和侵袭有关，并且与癌症患者的不良预后相关。然而，其在胶质瘤中的临床意义和生物学作用仍不清楚。在此，我们发现SMC4在胶质瘤细胞和临床组织中的mRNA和蛋白水平均显著升高，且与不良预后相关。SMC4的过表达在体外和体内均显著促进胶质瘤细胞的增殖率以及迁移和侵袭能力，而SMC4的下调则降低了这些能力。此外，在转导了SMC4的胶质瘤细胞中被激活而在沉默了SMC4的胶质瘤细胞中被抑制的转化生长因子β（TGFβ）/Smad信号通路，促成了SMC4介导的胶质瘤细胞侵袭性。我们的结果为SMC4的肿瘤功能以及TGFβ/Smad通路在胶质瘤中过度激活的机制提供了新的见解，表明SMC4是胶质瘤中一个有价值的预后因素和潜在的治疗靶点。
