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首页> 外文期刊>Cellular Signalling >TCEA3 binds to TGF-beta receptor I and induces Smad-independent, JNK-dependent apoptosis in ovarian cancer cells
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TCEA3 binds to TGF-beta receptor I and induces Smad-independent, JNK-dependent apoptosis in ovarian cancer cells

机译:TCEA3与TGF-β受体I结合并诱导卵巢癌细胞中Smad依赖性,JNK依赖性凋亡

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摘要

TFIIS is a transcription elongation factor conserved in frog, mouse and human. Recently, knockdown of TCEA1, the most well-characterized isoform of TFIIS, by RNA silencing was reported to inhibit cancer cell proliferation and induce apoptosis in breast, lung and pancreatic cancer cell lines through activation of p53 (Hubbard et al., 2008 [1]). However, the functions of other TFIIS isoforms are poorly defined. The present study shows that TCEA3, an isoform of TFIIS, can trigger ovarian cancer-specific cell death by activating the JNK signaling pathway. TCEA3 expression is low in ovarian cancer cell lines compared to noncancerous ovarian epithelial cells. Suppression of TCEA3 in noncancerous ovarian epithelial cells promotes cell growth whereas ectopic expression of TCEA3 in ovarian cancer cell lines induces the caspase-dependent mitochondrial cell death pathway. Molecular and chemical inhibition assays show that the interaction of TCEA3 with TGFβ receptor I induces cell death in ovarian cancer cell through Smad-independent activation of the JNK pathway. These results reveal that TCEA3 induces a novel apoptotic mechanism in OEC, which provides TCEA3 as a novel target to develop therapeutics of ovarian cancer.
机译:TFIIS是在青蛙,小鼠和人类中保守的转录延伸因子。最近,据报道,通过RNA沉默可降低TCIIS的特征,即TFIIS的特征最丰富的同工型,可通过激活p53抑制癌细胞增殖并诱导乳腺癌,肺癌和胰腺癌细胞系凋亡(Hubbard等,2008 [1 ])。但是,其他TFIIS亚型的功能定义不清。本研究表明,TFIIS的同种型TCEA3可通过激活JNK信号通路触发卵巢癌特异性细胞死亡。与非癌性卵巢上皮细胞相比,TCEA3在卵巢癌细胞系中的表达较低。 TCEA3在非癌性卵巢上皮细胞中的抑制促进细胞生长,而TCEA3在卵巢癌细胞系中的异位表达诱导caspase依赖性线粒体细胞死亡途径。分子和化学抑​​制试验表明,TCEA3与TGFβ受体I的相互作用通过Smad依赖性的JNK途径活化,诱导卵巢癌细胞死亡。这些结果表明,TCEA3在OEC中诱导了一种新的凋亡机制,这为TCEA3提供了开发卵巢癌治疗剂的新靶标。

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