HTERT promotes tumor angiogenesis by activating VEGF via interactions with the Sp1 transcription factor

Ning Liu, Deqiang Ding, Wanyu Hao, Fan Yang, Xiaoying Wu, Miao Wang, Xiaoling Xu, Zhenyu Ju, Jun Ping Liu, Zhangfa Song, Jerry W. Shay, Yunliang Guo, Yu Sheng Cong

Research output: Contribution to journalArticle

33 Scopus citations

Abstract

Angiogenesis is recognized as an important hallmark of cancer. Although telomerase is thought to be involved in tumor angiogenesis, the evidence and underlying mechanism remain elusive. Here, we demonstrate that human telomerase reverse transcriptase (hTERT) activates vascular epithelial growth factor (VEGF) gene expression through interactions with the VEGF promoter and the transcription factor Sp1. hTERT binds to Sp1 in vitro and in vivo and stimulates angiogenesis in a manner dependent on Sp1. Deletion of the mTert gene in the first generation of Tert null mice compromised tumor growth, with reduced VEGF expression. In addition, we show that hTERT expression levels are positively correlated with those of VEGF in human gastric tumor samples. Together, our results demonstrate that hTERT facilitates tumor angiogenesis by up-regulating VEGF expression through direct interactions with the VEGF gene and the Sp1 transcription factor. These results provide novel insights into hTERT function in tumor progression in addition to its role in telomere maintenance.

Original languageEnglish (US)
Pages (from-to)8693-8703
Number of pages11
JournalNucleic acids research
Volume44
Issue number18
DOIs
StatePublished - Oct 14 2016

ASJC Scopus subject areas

  • Genetics

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    Liu, N., Ding, D., Hao, W., Yang, F., Wu, X., Wang, M., Xu, X., Ju, Z., Liu, J. P., Song, Z., Shay, J. W., Guo, Y., & Cong, Y. S. (2016). HTERT promotes tumor angiogenesis by activating VEGF via interactions with the Sp1 transcription factor. Nucleic acids research, 44(18), 8693-8703. https://doi.org/10.1093/nar/gkw549