title: Human telomerase reverse transcriptase (hTERT) promotes gastric cancer invasion through cooperating with c-Myc to upregulate heparanase expression.
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/Î²-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.
authors.affiliation: Department of Gastroenterology, Xinqiao Hospital, Third Military Medical University, Chongqing 400037, China.|Department of Medicine, School of Medicine, University of California, San Diego, CA 92093, USA.
authors.forename: Bo
authors.initials: B
authors.lastname: Tang
authors.affiliation: Department of Gastroenterology, Xinqiao Hospital, Third Military Medical University, Chongqing 400037, China.
authors.forename: Rui
authors.initials: R
authors.lastname: Xie
authors.affiliation: Department of Gastroenterology, Xinqiao Hospital, Third Military Medical University, Chongqing 400037, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Qin
authors.affiliation: Department of Gastroenterology, Xinqiao Hospital, Third Military Medical University, Chongqing 400037, China.
authors.forename: Yu-Feng
authors.initials: YF
authors.lastname: Xiao
authors.affiliation: Department of Gastroenterology, Xinqiao Hospital, Third Military Medical University, Chongqing 400037, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Yong
authors.affiliation: Department of Gastroenterology, Xinqiao Hospital, Third Military Medical University, Chongqing 400037, China.|Department of Nuclear Medicine, Southwest Hospital, Third Military Medical University, Chongqing 400038, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Zheng
authors.affiliation: Department of Gastroenterology, Xinqiao Hospital, Third Military Medical University, Chongqing 400037, China.|Department of Medicine, School of Medicine, University of California, San Diego, CA 92093, USA.
authors.forename: Hui
authors.initials: H
authors.lastname: Dong
authors.affiliation: Department of Gastroenterology, Xinqiao Hospital, Third Military Medical University, Chongqing 400037, China.
authors.forename: Shi-Ming
authors.initials: SM
authors.lastname: Yang
mesh_terms: D000818:Animals; D005260:Female; D005966:Glucuronidase / Q000096:biosynthesis* / Q000235:genetics; D064593:Heterografts; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008875:Middle Aged; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics / Q000378:metabolism*; D013274:Stomach Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D019098:Telomerase / Q000235:genetics / Q000378:metabolism*; D014162:Transfection; D015854:Up-Regulation; D000099175:Heparanase
chemical_list: D005966:Glucuronidase; D016271:Proto-Oncogene Proteins c-myc; D019098:Telomerase; D000099175:Heparanase; C489427:MYC protein, human; C509186:TERT protein, human
keywords: c-Myc; gastric cancer; hTERT; heparanase; invasion