Glycolysis, via NADH-dependent dimerisation of CtBPs, regulates hypoxia-induced expression of CAIX and stem-like breast cancer cell survival
Glycolysis, via NADH-dependent dimerisation of CtBPs, regulates hypoxia-induced expression of CAIX and stem-like breast cancer cell survival
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 co-regulators 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.
NADH, breast cancer, carbonic anhydrase IX, glycolysis, hypoxia, stem cell-like cancer cells
2988-3001
Kreuzer, Mira Rosemarie
b6e55e12-45d4-4237-a42e-003f3493f956
Banerjee, Arindam
7e1217f4-949a-4851-be1a-c597e31a38b9
Birts, Charles
8689ddad-ba47-4ca6-82c5-001315dbd250
Darley, Matthew
7be23780-a781-4dd4-a74c-f5affbb79521
Tavassoli, Ali
d561cf8f-2669-46b5-b6e1-2016c85d63b2
Ivan, Mircea
5f528623-17bc-4b50-b2f4-a4aa45a89c90
Blaydes, Jeremy
e957f999-fd91-4f77-ad62-5b4ef069b15b
1 September 2020
Kreuzer, Mira Rosemarie
b6e55e12-45d4-4237-a42e-003f3493f956
Banerjee, Arindam
7e1217f4-949a-4851-be1a-c597e31a38b9
Birts, Charles
8689ddad-ba47-4ca6-82c5-001315dbd250
Darley, Matthew
7be23780-a781-4dd4-a74c-f5affbb79521
Tavassoli, Ali
d561cf8f-2669-46b5-b6e1-2016c85d63b2
Ivan, Mircea
5f528623-17bc-4b50-b2f4-a4aa45a89c90
Blaydes, Jeremy
e957f999-fd91-4f77-ad62-5b4ef069b15b
Kreuzer, Mira Rosemarie, Banerjee, Arindam, Birts, Charles, Darley, Matthew, Tavassoli, Ali, Ivan, Mircea and Blaydes, Jeremy
(2020)
Glycolysis, via NADH-dependent dimerisation of CtBPs, regulates hypoxia-induced expression of CAIX and stem-like breast cancer cell survival.
FEBS Letters, 594 (18), .
(doi:10.1002/1873-3468.13874).
Abstract
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 co-regulators 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.
Text
Kreuzer_CAIXv3.2_Author_accepted_with figures
- Accepted Manuscript
More information
Accepted/In Press date: 17 June 2020
e-pub ahead of print date: 3 July 2020
Published date: 1 September 2020
Additional Information:
Funding Information:
This study was supported by funds from the Institute of Life Sciences and School of Chemistry, University of Southampton, Breast Cancer Now (2014NovPR341) and Cancer Research UK (C34999/A18087). Charles Birts is now an Against Breast Cancer-funded lecturer at the School of Biological Sciences, University of Southampton.
Publisher Copyright:
© 2020 The Authors. FEBS Letters published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies
Keywords:
NADH, breast cancer, carbonic anhydrase IX, glycolysis, hypoxia, stem cell-like cancer cells
Identifiers
Local EPrints ID: 442077
URI: http://eprints.soton.ac.uk/id/eprint/442077
ISSN: 0014-5793
PURE UUID: 2b04bf6c-ba6c-41ab-89c8-4197c31fb992
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Date deposited: 07 Jul 2020 16:30
Last modified: 17 Mar 2024 05:42
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Contributors
Author:
Mira Rosemarie Kreuzer
Author:
Arindam Banerjee
Author:
Matthew Darley
Author:
Mircea Ivan
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