Tan Fen, Chen Juan, Sun Lunquan, Zhang Lu, Zhou Rui
Department of Critical Care Medicine, the Second Xiangya Hospital, Central South University, Changsha 410011, China.
Department of Pulmonary and Critical Care Medicine, Shenzhen People's Hospital, Shenzhen 518020, China.
Acta Biochim Biophys Sin (Shanghai). 2025 Apr 25;57(8):1292-1303. doi: 10.3724/abbs.2025049.
Connexins (Cxs), also known as gap junction proteins, are structurally related transmembrane proteins and have been implicated in carcinogenesis. Although some evidence suggests that these proteins are tumor suppressors due to their reduced expression in cancers, recent research indicates their complicated roles in tumor progression during different stages, including metastasis. Here, we show that Cx58, which is upregulated in non-small cell lung cancer (NSCLC), is modulated by myocyte-enhancer binding factor 2B (MEF2B). Either or knockdown attenuates the migration and invasion of NSCLC cells by inducing cytoskeleton rearrangement. Additionally, the prometastatic role of Cx58 in NSCLC is demonstrated . In conclusion, our findings suggest that Cx58 is transcriptionally activated by MEF2B and is involved in the metastasis of NSCLC by regulating cytoskeleton organization. Targeting the MEF2B/Cx58 axis may be exploited as a modality for improving NSCLC therapy.
连接蛋白(Cxs),也被称为间隙连接蛋白,是结构相关的跨膜蛋白,与肿瘤发生有关。尽管一些证据表明这些蛋白由于在癌症中表达降低而具有肿瘤抑制作用,但最近的研究表明它们在包括转移在内的肿瘤不同阶段进展中发挥着复杂的作用。在这里,我们表明在非小细胞肺癌(NSCLC)中上调的Cx58受肌细胞增强因子结合因子2B(MEF2B)调控。MEF2B或Cx58的敲低通过诱导细胞骨架重排减弱NSCLC细胞的迁移和侵袭。此外,还证明了Cx58在NSCLC中的促转移作用。总之,我们的研究结果表明Cx58被MEF2B转录激活,并通过调节细胞骨架组织参与NSCLC的转移。靶向MEF2B/Cx58轴可能被开发为改善NSCLC治疗的一种方式。