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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
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.
0014-5793
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
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.

Record type: Article

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.

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Kreuzer_CAIXv3.2_Author_accepted_with figures - Accepted Manuscript
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Accepted/In Press date: 17 June 2020
e-pub ahead of print date: 3 July 2020

Identifiers

Local EPrints ID: 442077
URI: http://eprints.soton.ac.uk/id/eprint/442077
ISSN: 0014-5793
PURE UUID: 2b04bf6c-ba6c-41ab-89c8-4197c31fb992
ORCID for Arindam Banerjee: ORCID iD orcid.org/0000-0003-2292-4936
ORCID for Charles Birts: ORCID iD orcid.org/0000-0002-0368-8766
ORCID for Ali Tavassoli: ORCID iD orcid.org/0000-0002-7420-5063
ORCID for Jeremy Blaydes: ORCID iD orcid.org/0000-0001-8525-0209

Catalogue record

Date deposited: 07 Jul 2020 16:30
Last modified: 18 Feb 2021 17:07

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