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TERT promoter mutations and GABP transcription factors in carcinogenesis: More foes than friends.

Authors
  • Yuan, Xiaotian1
  • Dai, Mingkai2
  • Xu, Dawei3
  • 1 Center for Reproductive Medicine, Cheeloo College of Medicine, Shandong University, Jinan, 250012, PR China. Electronic address: [email protected] , (China)
  • 2 Central Research Laboratory, The Second Hospital, Cheeloo College of Medicine, Shandong University, Jinan, 250033, PR China; Shandong University-Karolinska Institute Collaborative Laboratory for Cancer and Stem Cell Research, Shandong University Second Hospital, Jinan, 250033, PR China. Electronic address: [email protected] , (China)
  • 3 Shandong University-Karolinska Institute Collaborative Laboratory for Cancer and Stem Cell Research, Shandong University Second Hospital, Jinan, 250033, PR China; Department of Medicine, Division of Hematology, Bioclinicum and Center for Molecular Medicine (CMM), Karolinska Institutet and Karolinska University Hospital Solna, 171 64 Solna, Sweden. Electronic address: [email protected] , (China)
Type
Published Article
Journal
Cancer letters
Publication Date
Aug 06, 2020
Volume
493
Pages
1–9
Identifiers
DOI: 10.1016/j.canlet.2020.07.003
PMID: 32768523
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

The transcriptional de-repression of the telomerase reverse transcriptase (TERT) gene and subsequent activation of telomerase is a prerequisite step in malignant transformation and progression. Recently, the gain-of-function mutation of the TERT promoter was identified in many types of human malignancies, and the mutated promoter acquires de novo ETS binding motifs through which the TERT transcription is activated. The ETS family transcription factors GABPA and GABPB1 have been shown to act as master drivers for the mutant TERT promoter activity. Indeed, GABPA or GABPB1 depletion leads to the down-regulation of TERT expression in the mutant TERT promoter-bearing cancer cells, and is thus proposed as targets for cancer therapy. Surprisingly, however, despite its key role in activating the mutant TERT promoter and telomerase, GABPA may itself function as a potent tumor suppressor in several malignancies. In this review, we address the collaboration between GABPA and mutant TERT promoter in cancer development, discuss selection trade-offs among different activities of GABPA in cancer evolution, and underscore the suppressive function of GABPA in cancer progression and implications in precision oncology. Copyright © 2020 The Authors. Published by Elsevier B.V. All rights reserved.

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