Glycolysis, via NADH-dependent dimerisation of CtBPs, regulates hypoxia-induced expression of CAIX and stem-like breast cancer cell survival.
Alcohol Oxidoreductases
/ genetics
Breast Neoplasms
/ genetics
Cell Hypoxia
/ genetics
DNA-Binding Proteins
/ genetics
Female
Gene Expression Regulation, Enzymologic
Gene Expression Regulation, Neoplastic
Glycolysis
Humans
MCF-7 Cells
NAD
/ genetics
Neoplasm Proteins
/ genetics
Neoplastic Stem Cells
/ metabolism
Nerve Tissue Proteins
/ genetics
Protein Multimerization
NADH
breast cancer
carbonic anhydrase IX
glycolysis
hypoxia
stem cell-like cancer cells
Journal
FEBS letters
ISSN: 1873-3468
Titre abrégé: FEBS Lett
Pays: England
ID NLM: 0155157
Informations de publication
Date de publication:
09 2020
09 2020
Historique:
received:
30
08
2019
revised:
12
06
2020
accepted:
17
06
2020
pubmed:
4
7
2020
medline:
12
5
2021
entrez:
4
7
2020
Statut:
ppublish
Résumé
Adaptive responses to hypoxia are mediated by the hypoxia-inducible factor (HIF) family of transcription factors. These responses include the upregulation of glycolysis to maintain ATP production. This also generates acidic metabolites, which require HIF-induced carbonic anhydrase IX (CAIX) for their neutralisation. C-terminal binding proteins (CtBPs) are coregulators of gene transcription and couple glycolysis with gene transcription due to their regulation by the glycolytic coenzyme NADH. Here, we find that experimental manipulation of glycolysis and CtBP function in breast cancer cells through multiple complementary approaches supports a hypothesis whereby the expression of known HIF-inducible genes, and CAIX in particular, adapts to available glucose in the microenvironment through a mechanism involving CtBPs. This novel pathway promotes the survival of stem cell-like cancer (SCLC) cells in hypoxia.
Identifiants
pubmed: 32618367
doi: 10.1002/1873-3468.13874
doi:
Substances chimiques
CA10 protein, human
0
DNA-Binding Proteins
0
Neoplasm Proteins
0
Nerve Tissue Proteins
0
NAD
0U46U6E8UK
Alcohol Oxidoreductases
EC 1.1.-
C-terminal binding protein
EC 1.1.1.-
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
2988-3001Subventions
Organisme : Breast Cancer Now
ID : 2014NOVPR341
Pays : United Kingdom
Organisme : Cancer Research UK
ID : C34999/A18087
Pays : United Kingdom
Informations de copyright
© 2020 The Authors. FEBS Letters published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.
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