Journal
NATURE REVIEWS GASTROENTEROLOGY & HEPATOLOGY
Volume 16, Issue 9, Pages 544-558Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/s41575-019-0165-3
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Funding
- Institut National du Cancer (INCa)
- International Cancer Genome Consortium (ICGC LICA-FR project)
- NoFLIC project (PAIR HCC)
- NoFLIC project (INCa)
- NoFLIC project (ARC)
- INSERM
- Cancer et Environnement (plan Cancer)
- MUTHEC projects (INCa)
- TELOTHEP project (PRTK2017 INCA)
- HETCOLI project (Tumor Heterogeneity)
- HETCOLI project (Ecosystem Program)
- Ligue Nationale contre le Cancer (Equipe Labellisee)
- Labex OncoImmunology (investissement d'avenir)
- Coup d'Elan de la Fondation Bettencourt-Shueller
- SIRIC CARPEM
- Fondation Merieux
- Prix Duquesne (Ligue Contre le Cancer, Comite de Paris)
- Prix Raymond Rosen (Fondation pour la Recherche Medicale)
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Telomerase is a key enzyme for cell survival that prevents telomere shortening and the subsequent cellular senescence that is observed after many rounds of cell division. In contrast, inactivation of telomerase is observed in most cells of the adult liver. Absence of telomerase activity and shortening of telomeres has been implicated in hepatocyte senescence and the development of cirrhosis, a chronic liver disease that can lead to hepatocellular carcinoma (HCC) development. During hepatocarcinogenesis, telomerase reactivation is required to enable the uncontrolled cell proliferation that leads to malignant transformation and HCC development. Part of the telomerase complex, telomerase reverse transcriptase, is encoded by TERT, and several mechanisms of telomerase reactivation have been described in HCC that include somatic TERT promoter mutations, TERT amplification, TERT translocation and viral insertion into the TERT gene. An understanding of the role of telomeres and telomerase in HCC development is important to develop future targeted therapies and improve survival of this disease. In this Review, the roles of telomeres and telomerase in liver carcinogenesis are discussed, in addition to their potential translation to clinical practice as biomarkers and therapeutic targets.
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