Liu Ke, Jiao Xiao-Dong, Hao Jie-Lu, Qin Bao-Dong, Wu Ying, Chen Wei, Liu Jun, He Xi, Zang Yuan-Sheng
Department of Medical Oncology, Changzheng Hospital, Naval Medical University, Shanghai, People's Republic of China.
Department of Nephrology, Changzheng Hospital, Naval Medical University, Shanghai, People's Republic of China.
Onco Targets Ther. 2019 Jul 2;12:5143-5152. doi: 10.2147/OTT.S203165. eCollection 2019.
Metastasis suppressor 1 (MTSS1), a potential metastasis suppressor gene associated with tumor progression, may play an important role in cancer development. Our previous study demonstrated that MTSS1 was downregulated significantly when gastric cancer (GC) progressed and metastasized, suggesting that MTSS1 may be involved in the physiopathologic mechanism of GC. The objective of this study was to evaluate the effect of MTSS1 expression on the biological behavior of gastric cancer cell both and . The gain-and-loss function of MTSS1 in GC cells were analyzed after transfection with pEGFP-N1-MTSS1 and ShRNA431. Proliferation and invasion abilities were measured by means of plate clone formation assay and transwell assay. To further explore the underlying mechanism of MTSS1-induced tumor restrain, cell cycle distribution was analyzed using flow cytometry. The results revealed that overexpression of MTSS1 significantly reduced proliferation, migration and invasion of GC cells and , while downregulation of MTSS1 had the opposite biological manifestations. Moreover, overexpression of MTSS1 induced accumulation of GC cells in G2/M phase, increased phosphorylated Cdc2 expression and decreased Cdc25C and cyclinB1 levels, suggesting MTSS1 could cause G2/M cell cycle arrest. Our data provided insight into an important role for MTSS1 in suppressing tumor cell proliferation, invasion and migration, indicating that MTSS, as a functional tumor suppressor in GC, could be a potential therapeutic target to prevent GC metastasis.
转移抑制因子1(MTSS1)是一种与肿瘤进展相关的潜在转移抑制基因,可能在癌症发展中起重要作用。我们之前的研究表明,在胃癌(GC)进展和转移时,MTSS1表达显著下调,提示MTSS1可能参与了胃癌的生理病理机制。本研究的目的是评估MTSS1表达对胃癌细胞生物学行为的影响。在用pEGFP-N1-MTSS1和ShRNA431转染后,分析MTSS1在GC细胞中的得失功能。通过平板克隆形成试验和Transwell试验检测增殖和侵袭能力。为了进一步探讨MTSS1诱导肿瘤抑制的潜在机制,使用流式细胞术分析细胞周期分布。结果显示,MTSS1的过表达显著降低了GC细胞的增殖、迁移和侵袭能力,而MTSS1的下调则具有相反的生物学表现。此外,MTSS1的过表达诱导GC细胞在G2/M期积累,增加磷酸化Cdc2表达并降低Cdc25C和细胞周期蛋白B1水平,提示MTSS1可导致G2/M期细胞周期阻滞。我们的数据揭示了MTSS1在抑制肿瘤细胞增殖、侵袭和迁移中的重要作用,表明MTSS作为胃癌中的一种功能性肿瘤抑制因子,可能是预防胃癌转移潜在的治疗靶点。