Exploring the Interplay of Telomerase Reverse Transcriptase and β-Catenin in Hepatocellular Carcinoma
Department of Oncological Sciences, Department of Pathology, and Huntsman Cancer Institute, University of Utah, Salt Lake City, UT 84112, USA
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Author to whom correspondence should be addressed.
Academic Editor: Jens Marquardt
Cancers 2021, 13(16), 4202; https://doi.org/10.3390/cancers13164202
Received: 26 June 2021
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Revised: 12 August 2021
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Accepted: 15 August 2021
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Published: 20 August 2021
Simple Summary
Liver cancer is one of the deadliest human cancers. Two of the most common molecular aberrations in liver cancer are: (1) activating mutations in the gene encoding β-catenin (CTNNB1); and (2) promoter mutations in telomerase reverse transcriptase (TERT). Here, we review recent findings regarding the interplay between TERT and β-catenin in order to better understand their role in liver cancer.
Hepatocellular carcinoma (HCC) is one of the deadliest human cancers. Activating mutations in the telomerase reverse transcriptase (TERT) promoter (TERTp) and CTNNB1 gene encoding β-catenin are widespread in HCC (~50% and ~30%, respectively). TERTp mutations are predicted to increase TERT transcription and telomerase activity. This review focuses on exploring the role of TERT and β-catenin in HCC and the current findings regarding their interplay. TERT can have contradictory effects on tumorigenesis via both its canonical and non-canonical functions. As a critical regulator of proliferation and differentiation in progenitor and stem cells, activated β-catenin drives HCC; however, inhibiting endogenous β-catenin can also have pro-tumor effects. Clinical studies revealed a significant concordance between TERTp and CTNNB1 mutations in HCC. In stem cells, TERT acts as a co-factor in β-catenin transcriptional complexes driving the expression of WNT/β-catenin target genes, and β-catenin can bind to the TERTp to drive its transcription. A few studies have examined potential interactions between TERT and β-catenin in HCC in vivo, and their results suggest that the coexpression of these two genes promotes hepatocarcinogenesis. Further studies are required with vertebrate models to better understand how TERT and β-catenin influence hepatocarcinogenesis.
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Keywords:
hepatocellular carcinoma; TERT; TERT promoter; β-catenin
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MDPI and ACS Style
Kotiyal, S.; Evason, K.J. Exploring the Interplay of Telomerase Reverse Transcriptase and β-Catenin in Hepatocellular Carcinoma. Cancers 2021, 13, 4202. https://doi.org/10.3390/cancers13164202
AMA Style
Kotiyal S, Evason KJ. Exploring the Interplay of Telomerase Reverse Transcriptase and β-Catenin in Hepatocellular Carcinoma. Cancers. 2021; 13(16):4202. https://doi.org/10.3390/cancers13164202
Chicago/Turabian StyleKotiyal, Srishti, and Kimberley J. Evason. 2021. "Exploring the Interplay of Telomerase Reverse Transcriptase and β-Catenin in Hepatocellular Carcinoma" Cancers 13, no. 16: 4202. https://doi.org/10.3390/cancers13164202
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