Cancer is one of the most fatal diseases that threaten human health, whereas more than 90% mortality of cancer patients is caused by tumor metastasis, rather than the growth of primary tumors. Thus, how to effectively control or even reverse the migration of tumor cells is of great significance for cancer therapy. CtBP, a transcriptional cofactor displaying high expression in a variety of human cancers, has become one of the main targets for cancer prediction, diagnosis, and treatment. The roles of CtBP in promoting tumorigenesis have been well studied in vitro, mostly based on gain-of-function, while its physiological functions in tumor invasion and the underlying mechanism remain largely elusive. Snail (Sna) is a well-known transcription factor involved in epithelial-to-mesenchymal transition (EMT) and tumor invasion, yet the mechanism that regulates Sna activity has not been fully understood. Using Drosophila as a model organism, we found that depletion of CtBP or snail (sna) suppressed Ras^V12/lgl^-/--triggered tumor growth and invasion, and disrupted cell polarity-induced invasive cell migration. In addition, loss of CtBP inhibits Ras^V12/Sna-induced tumor invasion and Sna-mediated invasive cell migration. Furthermore, both CtBP and Sna are physiologically required for developmental cell migration during thorax closure. Finally, Sna activates the JNK signaling and promotes JNK-dependent cell invasion. Given that CtBP physically interacts with Sna, our data suggest that CtBP and Sna may form a transcriptional complex that regulates JNK-dependent tumor invasion and cell migration in vivo.

癌症是威胁人类健康最致命的疾病之一，而癌症患者90%以上的死亡率是由肿瘤转移而不是原发肿瘤的生长引起的。因此，如何有效控制甚至逆转肿瘤细胞的迁移对于癌症治疗具有重要意义。CtBP 是一种在多种人类癌症中高表达的转录辅因子，已成为癌症预测、诊断和治疗的主要靶点之一。CtBP 在促进肿瘤发生中的作用已在体外得到很好的研究，主要基于功能获得，而其在肿瘤侵袭中的生理功能和潜在机制仍然难以捉摸。Snail (Sna) 是一种众所周知的转录因子，参与上皮间质转化 (EMT) 和肿瘤侵袭，然而，调节 Sna 活动的机制尚未完全了解。使用果蝇作为模式生物，我们发现CtBP或蜗牛( sna ) 的消耗抑制了 Ras ^V12 / lgl ^-/-触发的肿瘤生长和侵袭，并破坏了细胞极性诱导的侵袭性细胞迁移。此外，CtBP 的缺失会抑制 Ras ^V12/Sna 诱导的肿瘤侵袭和 Sna 介导的侵袭性细胞迁移。此外，在胸部闭合期间，CtBP 和 Sna 在生理上都是发育细胞迁移所必需的。最后，Sna 激活 JNK 信号并促进 JNK 依赖性细胞侵袭。鉴于 CtBP 与 Sna 物理相互作用，我们的数据表明 CtBP 和 Sna 可能形成转录复合物，在体内调节 JNK 依赖性肿瘤侵袭和细胞迁移。