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

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 cance...

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Autores principales: Tang, Bo, Xie, Rui, Qin, Yong, Xiao, Yu-Feng, Yong, Xin, Zheng, Lei, Dong, Hui, Yang, Shi-Ming
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4905479/
https://www.ncbi.nlm.nih.gov/pubmed/26689987
http://dx.doi.org/10.18632/oncotarget.6575
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author Tang, Bo
Xie, Rui
Qin, Yong
Xiao, Yu-Feng
Yong, Xin
Zheng, Lei
Dong, Hui
Yang, Shi-Ming
author_facet Tang, Bo
Xie, Rui
Qin, Yong
Xiao, Yu-Feng
Yong, Xin
Zheng, Lei
Dong, Hui
Yang, Shi-Ming
author_sort Tang, Bo
collection PubMed
description 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.
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spelling pubmed-49054792016-06-24 Human telomerase reverse transcriptase (hTERT) promotes gastric cancer invasion through cooperating with c-Myc to upregulate heparanase expression Tang, Bo Xie, Rui Qin, Yong Xiao, Yu-Feng Yong, Xin Zheng, Lei Dong, Hui Yang, Shi-Ming Oncotarget Research Paper 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. Impact Journals LLC 2015-12-11 /pmc/articles/PMC4905479/ /pubmed/26689987 http://dx.doi.org/10.18632/oncotarget.6575 Text en Copyright: © 2016 Tang et al. http://creativecommons.org/licenses/by/2.5/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Paper
Tang, Bo
Xie, Rui
Qin, Yong
Xiao, Yu-Feng
Yong, Xin
Zheng, Lei
Dong, Hui
Yang, Shi-Ming
Human telomerase reverse transcriptase (hTERT) promotes gastric cancer invasion through cooperating with c-Myc to upregulate heparanase expression
title Human telomerase reverse transcriptase (hTERT) promotes gastric cancer invasion through cooperating with c-Myc to upregulate heparanase expression
title_full Human telomerase reverse transcriptase (hTERT) promotes gastric cancer invasion through cooperating with c-Myc to upregulate heparanase expression
title_fullStr Human telomerase reverse transcriptase (hTERT) promotes gastric cancer invasion through cooperating with c-Myc to upregulate heparanase expression
title_full_unstemmed Human telomerase reverse transcriptase (hTERT) promotes gastric cancer invasion through cooperating with c-Myc to upregulate heparanase expression
title_short Human telomerase reverse transcriptase (hTERT) promotes gastric cancer invasion through cooperating with c-Myc to upregulate heparanase expression
title_sort human telomerase reverse transcriptase (htert) promotes gastric cancer invasion through cooperating with c-myc to upregulate heparanase expression
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4905479/
https://www.ncbi.nlm.nih.gov/pubmed/26689987
http://dx.doi.org/10.18632/oncotarget.6575
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