Human telomerase reverse transcriptase (hTERT) promotes gastric cancer invasion through cooperating with c-Myc to upregulate heparanase expression

// Bo Tang 1, 2 , Rui Xie 1 , Yong Qin 1 , Yu-Feng Xiao 1 , Xin Yong 1 , Lei Zheng 1, 3 , Hui Dong 1, 2 , Shi-Ming Yang 1 1 Department of Gastroenterology, Xinqiao Hospital, Third Military Medical University, Chongqing 400037, China 2 Department of Medicine, School of Medicine, University of California, San Diego, CA 92093, USA 3 Department of Nuclear Medicine, Southwest Hospital, Third Military Medical University, Chongqing 400038, China Correspondence to: Shi-Ming Yang, e-mail: shimingyang@yahoo.com Keywords: hTERT, heparanase, gastric cancer, invasion, c-Myc Received: August 09, 2015      Accepted: November 25, 2015      Published: December 11, 2015 ABSTRACT 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/I²-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.