An hTERT/ZEB1 complex directly regulates E-cadherin to promote epithelial-to-mesenchymal transition (EMT) in colorectal cancer.
An hTERT/ZEB1 complex directly regulates E-cadherin to promote epithelial-to-mesenchymal transition (EMT) in colorectal cancer.
复制标题
hTERT/ZEB1 复合物直接调节 E-钙粘蛋白促进结直肠癌上皮间质转化 (EMT)
DOI：
10.18632/oncotarget.5968
复制
发表时间：
2016-01-05
期刊：
影响因子：
--
通讯作者：
Yang SM
中科院分区：
文献类型：
--
作者：
Qin Y;Tang B;Hu CJ;Xiao YF;Xie R;Yong X;Wu YY;Dong H;Yang SM
在人类癌症中，端粒酶的高表达与肿瘤的侵袭性和转移潜能有关。端粒酶的激活是通过端粒酶逆转录酶(HTERT)的诱导来实现的，hTERT通过稳定端粒而导致恶性转化。已有研究表明，hTERT可促进胃癌、肝癌、食道癌等肿瘤的侵袭转移。上皮向间充质转化(EMT)是肿瘤侵袭和转移的必要条件，在肿瘤的发展过程中起着关键作用。虽然hTERT在几种癌症中通过Wnt信号促进EMT，但是否涉及其他信号通路尚不清楚。在本研究中，我们发现hTERT和ZEB1形成一个复合体，直接与E-钙粘蛋白启动子结合，进而抑制E-钙粘蛋白的表达，促进结直肠癌细胞的EMT。HTERT在HCT116和SW480细胞中过表达可诱导E-钙粘蛋白表达下调。然而，即使在hTERT过表达的情况下，当ZEB1功能受损时，E-cadherin的表达也可以恢复。综上所述，我们的研究结果表明，hTERT通过ZEB1途径刺激EMT，从而促进肿瘤转移，从而抑制它们可能阻止肿瘤进展。
In human cancer, high telomerase expression is correlated with tumor aggressiveness and metastatic potential. Telomerase activation occurs through telomerase reverse transcriptase (hTERT) induction, which contributes to malignant transformation by stabilizing telomeres. Previous studies have shown that hTERT can promote tumor invasion and metastasis of gastric cancer, liver cancer and esophageal cancer. Epithelial-to-mesenchymal transition (EMT), a requirement for tumor invasion and metastasis, plays a key role in cancer progression. Although hTERT promotes EMT through Wnt signaling in several cancers, it is unknown if other signaling pathways are involved. In the present study, we found that hTERT and ZEB1 form a complex, which directly binds to the E-cadherin promoter, and then inhibits E-cadherin expression and promots EMT in colorectal cancer cells. hTERT overexpression in HCT116 and SW480 cells could induce E-cadherin down-regulation. However, E-cadherin expression was recovered when ZEB1 function was impaired even during hTERT overexpression. Taken together, our findings suggest that hTERT can promote cancer metastasis by stimulating EMT through the ZEB1 pathway and therefore inhibiting them may prevent cancer progression.