Fumarate hydratase in cancer: A multifaceted tumour suppressor.
Cancer
FH
Fumarate
Metabolism
Mitochondria
Journal
Seminars in cell & developmental biology
ISSN: 1096-3634
Titre abrégé: Semin Cell Dev Biol
Pays: England
ID NLM: 9607332
Informations de publication
Date de publication:
02 2020
02 2020
Historique:
received:
12
03
2019
revised:
03
05
2019
accepted:
06
05
2019
pubmed:
16
5
2019
medline:
23
12
2020
entrez:
16
5
2019
Statut:
ppublish
Résumé
Cancer is now considered a multifactorial disorder with different aetiologies and outcomes. Yet, all cancers share some common molecular features. Among these, the reprogramming of cellular metabolism has emerged as a key player in tumour initiation and progression. The finding that metabolic enzymes such as fumarate hydratase (FH), succinate dehydrogenase (SDH) and isocitrate dehydrogenase (IDH), when mutated, cause cancer suggested that metabolic dysregulation is not only a consequence of oncogenic transformation but that it can act as cancer driver. However, the mechanisms underpinning the link between metabolic dysregulation and cancer remain only partially understood. In this review we discuss the role of FH loss in tumorigenesis, focusing on the role of fumarate as a key activator of a variety of oncogenic cascades. We also discuss how these alterations are integrated and converge towards common biological processes. This review highlights the complexity of the signals elicited by FH loss, describes that fumarate can act as a bona fide oncogenic event, and provides a compelling hypothesis of the stepwise neoplastic progression after FH loss.
Identifiants
pubmed: 31085323
pii: S1084-9521(18)30202-7
doi: 10.1016/j.semcdb.2019.05.002
pmc: PMC6974395
mid: EMS82869
pii:
doi:
Substances chimiques
Fumarate Hydratase
EC 4.2.1.2
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
15-25Subventions
Organisme : Medical Research Council
ID : MC_UU_12022/6
Pays : United Kingdom
Informations de copyright
Copyright © 2019. Published by Elsevier Ltd.
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