Cited by 674Cancer, Hypoxia, and MetabolismMitochondrial Function and PathologyFerroptosis and cancer prognosis

The DOI matches its Crossref record; 61 of the 61 references it cites were found in a registry or an index.

Succinate dehydrogenase and fumarate hydratase: linking mitochondrial dysfunction and cancer

King, A, Selak, M A, Gottlieb, E·2006·Oncogene

Abstract

The phenomenon of enhanced glycolysis in tumours has been acknowledged for decades, but biochemical evidence to explain it is only just beginning to emerge. A significant hint as to the triggers and advantages of enhanced glycolysis in tumours was supplied by the recent discovery that succinate dehydrogenase (SDH) and fumarate hydratase (FH) are tumour suppressors and which associated, for the first time, mitochondrial enzymes and their dysfunction with tumorigenesis. Further steps forward showed that the substrates of SDH and FH, succinate and fumarate, respectively, can mediate a 'metabolic signalling' pathway. Succinate or fumarate, which accumulate in mitochondria owing to the inactivation of SDH or FH, leak out to the cytosol, where they inhibit a family of prolyl hydroxylase enzymes (PHDs). Depending on the PHD inhibited, two newly recognized pathways that support tumour maintenance may ensue: affected cells become resistant to certain apoptotic signals and/or activate a pseudohypoxic response that enhances glycolysis and is conveyed by hypoxia-inducible factor.

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Crossref · 10.1038/sj.onc.1209594

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Metadata

Authors
King, A., Selak, M. A., & Gottlieb, E.
Affiliations
Cancer Research UK Scotland Institute (GB)
Corresponding author
Gottlieb, E
Venue
Oncogene
Published
2006-08-07
Volume
25
Issue
34
Pages
4675-4682
ISSN
  • 0950-9232 (ISSN-L)
  • 1476-5594
OpenAlex
W2005828644
Cited by
672
References
61
Citations by year
2026: 21 · 2025: 22 · 2024: 19 · 2023: 25 · 2022: 42 · 2021: 39 · 2020: 38 · 2019: 37 · 2018: 37 · 2017: 42 · 2016: 39 · 2015: 37 · 2014: 42 · 2013: 37 · 2012: 52
FWCI
1.59
Type
journal article
Language
en
Open access
closed
Locations
  • Oncogene (publishedVersion)
  • PubMed (publishedVersion)
  • ENLIGHTEN (Jurnal Bimbingan dan Konseling Islam) (submittedVersion)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Ferroptosis and cancer prognosis
Keywords
succinate dehydrogenase, fumarate hydratase, mitochondrial dysfunction, tumour suppressor, succinic acid, fumarate, metabolic signalling, prolyl hydroxylase inhibition, pseudohypoxia, hypoxia-inducible factor, apoptosis resistance, carcinogenesis
MeSH terms
Fumarate Hydratase, Humans, Mitochondria, Neoplasms, Succinate Dehydrogenase, Genes, Tumor Suppressor

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