CtBP modulates Snail-mediated tumor invasion in Drosophila.
CtBP modulates Snail-mediated tumor invasion in Drosophila.
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CtBP 调节果蝇 Snail 介导的肿瘤侵袭
DOI：
10.1038/s41420-021-00516-x
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发表时间：
2021-08-04
影响因子：
7
通讯作者：
Xue L
中科院分区：
文献类型：
--
作者：
Wu C;Ding X;Li Z;Huang Y;Xu Q;Zou R;Zhao M;Chang H;Jiang C;La X;Lin G;Li W;Xue L
癌症是威胁人类健康的最致命疾病之一，而癌症患者90%以上的死亡率是由肿瘤转移引起的，而不是由原发肿瘤的生长引起的。因此，如何有效地控制甚至逆转肿瘤细胞的迁移对于肿瘤的治疗具有重要意义。CTBP是一种在多种人类肿瘤中高表达的转录辅助因子，已成为肿瘤预测、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经在体外得到了很好的研究，主要是基于功能获得，但它在肿瘤侵袭中的生理功能和潜在的机制仍然很不清楚。Snail(Snail，SNA)是一种众所周知的转录因子，参与上皮间充质转化(EMT)和肿瘤侵袭，但其调节SNA活性的机制尚不完全清楚。以果蝇为模型生物，我们发现CtBP或蜗牛(SNA)的缺失抑制了RasV12/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的缺失抑制了RasV12/SNA诱导的肿瘤侵袭和SNA介导的侵袭性细胞迁移。此外，CtBP和SNA都是胸廓关闭过程中发育细胞迁移所必需的生理条件。最后，SNA激活JNK信号通路，促进JNK依赖的细胞侵袭。鉴于CtBP与SNA在物理上相互作用，我们的数据表明CtBP和SNA可能形成一个转录复合体，调节体内依赖JNK的肿瘤侵袭和细胞迁移。
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 RasV12/lgl-/--triggered tumor growth and invasion, and disrupted cell polarity-induced invasive cell migration. In addition, loss of CtBP inhibits RasV12/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.
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影响因子：
8
作者：
Grooteclaes, ML;Frisch, SM
通讯作者：
Frisch, SM
影响因子：
2.7
作者：
Hemavathy, K;Hu, XD;Ip, YT
通讯作者：
Ip, YT
影响因子：
8.8
作者：
Gerlach, Stephan U.;Eichenlaub, Teresa;Herranz, Hector
通讯作者：
Herranz, Hector
DOI：
10.1158/1078-0432.ccr-13-3173
发表时间：
2015-03-01
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Jung HY;Fattet L;Yang J
通讯作者：
Yang J
一种基于多功能φC31的记者系统，用于测量果蝇和组织培养中的AP-1和NRF2信号传导。
影响因子：
3.7
作者：
Chatterjee N;Bohmann D
通讯作者：
Bohmann D