Zhang Xin, Wang Linghui, Zeng Xianlu, Fujita Takashi, Liu Wenguang
The Key Laboratory of Molecular Epigenetics of MOE, Institute of Genetics and Cytology, Northeast Normal University, Changchun, Jilin 130024, China.
Department of Pharmaceutical Sciences, Molecular Toxicology Lab, Ritsumeikan University, Shiga 525-8577, Japan.
Cell Biol Int. 2017 Sep;41(9):1048-1055. doi: 10.1002/cbin.10824. Epub 2017 Jul 27.
The transcription factor Runx3 is a known tumor suppressor gene, and its expression is frequently lost in melanoma. However, the potential contribution of the loss of Runx3 expression to melanoma development and progression remains unclear. In this in vitro study, we demonstrated that ectopic Runx3 re-expression in B16-F10 melanoma cells changed the cell shape from elongated and branched to spread and unbranched, which enhanced stress fiber formation, increased the number of mature and fibrillar focal adhesions, and up-regulated fibronectin expression. In association with the cell shape change, the Runx3 re-expression in B16-F10 melanoma cells inhibited cell migration. Moreover, the phenotype of the Runx3 induced cell shape change was partially resembled when the melanoma cells were cultured on a fibronectin-coated coverslip, suggesting that fibronectin may mediate the Runx3 induced cell shape change of the melanoma cells. Taken together, our findings suggest that Runx3 may regulate cell shape to inhibit melanoma cell migration partly through enhancing stress fiber formation and ECM protein production. Our present study provides further evidence for the idea that cell shape change is potentially correlated with melanoma development and progression.
转录因子Runx3是一种已知的肿瘤抑制基因，其表达在黑色素瘤中常常缺失。然而，Runx3表达缺失对黑色素瘤发生和进展的潜在作用仍不清楚。在这项体外研究中，我们证明在B16-F10黑色素瘤细胞中异位重新表达Runx3会使细胞形态从细长和分支状变为铺展和无分支状，这增强了应力纤维的形成，增加了成熟和纤维状黏着斑的数量，并上调了纤连蛋白的表达。与细胞形态变化相关，B16-F10黑色素瘤细胞中Runx3的重新表达抑制了细胞迁移。此外，当黑色素瘤细胞在纤连蛋白包被的盖玻片上培养时，Runx3诱导的细胞形态变化的表型部分相似，这表明纤连蛋白可能介导了Runx3诱导的黑色素瘤细胞形态变化。综上所述，我们的研究结果表明，Runx3可能通过增强应力纤维形成和细胞外基质蛋白产生来调节细胞形态，从而部分抑制黑色素瘤细胞迁移。我们目前的研究为细胞形态变化可能与黑色素瘤发生和进展相关这一观点提供了进一步的证据。
