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Glycolysis, via NADH-dependent dimerisation of CtBPs, regulates hypoxia-induced expression of CAIX and stem-like breast cancer cell survival.
FEBS Lett. 2020 Jul 03 [Online ahead of print]FL

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 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.

Authors+Show Affiliations

Cancer Sciences Unit, Faculty of Medicine, University of Southampton, Southampton, Hants, UK. Institute for Life Sciences, University of Southampton, Southampton, Hants, UK.Cancer Sciences Unit, Faculty of Medicine, University of Southampton, Southampton, Hants, UK.Cancer Sciences Unit, Faculty of Medicine, University of Southampton, Southampton, Hants, UK. Institute for Life Sciences, University of Southampton, Southampton, Hants, UK.Cancer Sciences Unit, Faculty of Medicine, University of Southampton, Southampton, Hants, UK.Institute for Life Sciences, University of Southampton, Southampton, Hants, UK. School of Chemistry, University of Southampton, Southampton, Hants, UK.Indiana University School of Medicine, Indianapolis, Indiana, USA.Cancer Sciences Unit, Faculty of Medicine, University of Southampton, Southampton, Hants, UK. Institute for Life Sciences, University of Southampton, Southampton, Hants, UK.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

32618367

Citation

Kreuzer, Mira, et al. "Glycolysis, Via NADH-dependent Dimerisation of CtBPs, Regulates Hypoxia-induced Expression of CAIX and Stem-like Breast Cancer Cell Survival." FEBS Letters, 2020.
Kreuzer M, Banerjee A, Birts CN, et al. Glycolysis, via NADH-dependent dimerisation of CtBPs, regulates hypoxia-induced expression of CAIX and stem-like breast cancer cell survival. FEBS Lett. 2020.
Kreuzer, M., Banerjee, A., Birts, C. N., Darley, M., Tavassoli, A., Ivan, M., & Blaydes, J. P. (2020). Glycolysis, via NADH-dependent dimerisation of CtBPs, regulates hypoxia-induced expression of CAIX and stem-like breast cancer cell survival. FEBS Letters. https://doi.org/10.1002/1873-3468.13874
Kreuzer M, et al. Glycolysis, Via NADH-dependent Dimerisation of CtBPs, Regulates Hypoxia-induced Expression of CAIX and Stem-like Breast Cancer Cell Survival. FEBS Lett. 2020 Jul 3; PubMed PMID: 32618367.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Glycolysis, via NADH-dependent dimerisation of CtBPs, regulates hypoxia-induced expression of CAIX and stem-like breast cancer cell survival. AU - Kreuzer,Mira, AU - Banerjee,Arindam, AU - Birts,Charles N, AU - Darley,Matthew, AU - Tavassoli,Ali, AU - Ivan,Mircea, AU - Blaydes,Jeremy P, Y1 - 2020/07/03/ PY - 2019/08/30/received PY - 2020/06/12/revised PY - 2020/06/17/accepted PY - 2020/7/4/pubmed PY - 2020/7/4/medline PY - 2020/7/4/entrez KW - NADH KW - breast cancer KW - carbonic anhydrase IX KW - glycolysis KW - hypoxia KW - stem cell-like cancer cells JF - FEBS letters JO - FEBS Lett. N2 - 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. SN - 1873-3468 UR - https://www.unboundmedicine.com/medline/citation/32618367/Glycolysis,_via_NADH-dependent_dimerisation_of_CtBPs,_regulates_hypoxia-induced_expression_of_CAIX_and_stem-like_breast_cancer_cell_survival L2 - https://doi.org/10.1002/1873-3468.13874 DB - PRIME DP - Unbound Medicine ER -
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