Human telomerase reverse transcriptase (hTERT) promotes gastric cancer invasion through cooperating with c-Myc to upregulate heparanase expression.
Human telomerase reverse transcriptase (hTERT) promotes gastric cancer invasion through cooperating with c-Myc to upregulate heparanase expression.
复制标题
人端粒酶逆转录酶(hTERT)通过与c-Myc协同上调乙酰肝素酶表达促进胃癌侵袭
DOI：
10.18632/oncotarget.6575
复制
发表时间：
2016-03-08
期刊：
影响因子：
--
通讯作者：
Yang SM
中科院分区：
文献类型：
--
作者：
Tang B;Xie R;Qin Y;Xiao YF;Yong X;Zheng L;Dong H;Yang SM
人端粒酶逆转录酶（Human telomerase reverse transcriptase，hTERT）是多种肿瘤标志物的中心调节因子。然而，hTERT在肿瘤侵袭和转移中的潜在作用及其分子机制仍知之甚少。在此，我们发现hTERT在胃癌（GC）中的表达与晚期TNM分期、淋巴结转移显著相关。生存分析表明hTERT是胃癌患者生存的独立预后因素。hTERT通过与c-Myc结合，募集hTERT复合物至乙酰肝素酶启动子，上调乙酰肝素酶的表达，从而促进胃癌细胞的侵袭和转移。此外，我们的数据表明，hTERT激活Wnt/β 2-catenin信号通路，促进c-Myc表达，c-Myc反过来又激活hTERT的转录和表达，提示在GC进展中存在正反馈调节。结论c-Myc和heparanase表达与hTERT水平呈正相关，是肿瘤转移和生存的独立预测因子。总的来说，我们的数据提供了一个新的分子机制，hTERT促进胃癌的侵袭和转移，并强调了hTERT在胃癌进展的分子病因学和临床意义。靶向hTERT可能代表一种新的治疗策略，以改善GC患者的治疗和生存。
Human telomerase reverse transcriptase (hTERT) is a central regulator of multiple hallmarks of tumors. However, the potential roles of hTERT in tumor invasion and metastasis and the underlying molecular mechanisms remain poorly understood. Here, we found that the expression of hTERT in gastric cancer (GC) was significantly associated with an advanced TNM stage, lymphatic metastasis. Survival analysis identified hTERT as an independent prognostic factor for survival of GC patients. hTERT promoted the invasion and metastasis of GC cells by binding to c-Myc and recruiting the complex to heparanase promoter to upregulate heparanase expression. In addition, our data demonstrated that hTERT activated Wnt/β-catenin signaling to promote c-Myc expression which could in turn activate hTERT transcription and expression, suggesting a positive feedback regulation in GC progression. Consistently, c-Myc and heparanase expression was positively correlated with hTERT levels, and was also an independent predictor of metastasis and survival. Collectively, our data provide a novel molecular mechanism for hTERT in promotion of GC invasion and metastasis, and highlight the molecular etiology and clinical significance of hTERT in GC progression. Targeting hTERT may represent a new therapeutic strategy to improve therapy and survival of GC patients.