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ZBTB7A acts as a tumor suppressor through the transcriptional repression of glycolysis

Elevated glycolysis is a common metabolic trait of cancer, but what drives such metabolic reprogramming remains incompletely clear. We report here a novel transcriptional repressor-mediated negative regulation of glycolysis. ZBTB7A, a member of the POK (POZ/BTB and Krüppel) transcription repressor f...

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Autores principales: Liu, Xue-Song, Haines, Jenna E., Mehanna, Elie K., Genet, Matthew D., Ben-Sahra, Issam, Asara, John M., Manning, Brendan D., Yuan, Zhi-Min
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cold Spring Harbor Laboratory Press 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4197949/
https://www.ncbi.nlm.nih.gov/pubmed/25184678
http://dx.doi.org/10.1101/gad.245910.114
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author Liu, Xue-Song
Haines, Jenna E.
Mehanna, Elie K.
Genet, Matthew D.
Ben-Sahra, Issam
Asara, John M.
Manning, Brendan D.
Yuan, Zhi-Min
author_facet Liu, Xue-Song
Haines, Jenna E.
Mehanna, Elie K.
Genet, Matthew D.
Ben-Sahra, Issam
Asara, John M.
Manning, Brendan D.
Yuan, Zhi-Min
author_sort Liu, Xue-Song
collection PubMed
description Elevated glycolysis is a common metabolic trait of cancer, but what drives such metabolic reprogramming remains incompletely clear. We report here a novel transcriptional repressor-mediated negative regulation of glycolysis. ZBTB7A, a member of the POK (POZ/BTB and Krüppel) transcription repressor family, directly binds to the promoter and represses the transcription of critical glycolytic genes, including GLUT3, PFKP, and PKM. Analysis of The Cancer Genome Atlas (TCGA) data sets reveals that the ZBTB7A locus is frequently deleted in many human tumors. Significantly, reduced ZBTB7A expression correlates with up-regulation of the glycolytic genes and poor survival in colon cancer patients. Remarkably, while ZBTB7A-deficient tumors progress exceedingly fast, they exhibit an unusually heightened sensitivity to glycolysis inhibition. Our study uncovers a novel tumor suppressor role of ZBTB7A in directly suppressing glycolysis.
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spelling pubmed-41979492015-03-01 ZBTB7A acts as a tumor suppressor through the transcriptional repression of glycolysis Liu, Xue-Song Haines, Jenna E. Mehanna, Elie K. Genet, Matthew D. Ben-Sahra, Issam Asara, John M. Manning, Brendan D. Yuan, Zhi-Min Genes Dev Research Paper Elevated glycolysis is a common metabolic trait of cancer, but what drives such metabolic reprogramming remains incompletely clear. We report here a novel transcriptional repressor-mediated negative regulation of glycolysis. ZBTB7A, a member of the POK (POZ/BTB and Krüppel) transcription repressor family, directly binds to the promoter and represses the transcription of critical glycolytic genes, including GLUT3, PFKP, and PKM. Analysis of The Cancer Genome Atlas (TCGA) data sets reveals that the ZBTB7A locus is frequently deleted in many human tumors. Significantly, reduced ZBTB7A expression correlates with up-regulation of the glycolytic genes and poor survival in colon cancer patients. Remarkably, while ZBTB7A-deficient tumors progress exceedingly fast, they exhibit an unusually heightened sensitivity to glycolysis inhibition. Our study uncovers a novel tumor suppressor role of ZBTB7A in directly suppressing glycolysis. Cold Spring Harbor Laboratory Press 2014-09-01 /pmc/articles/PMC4197949/ /pubmed/25184678 http://dx.doi.org/10.1101/gad.245910.114 Text en © 2014 Liu et al.; Published by Cold Spring Harbor Laboratory Press http://creativecommons.org/licenses/by-nc/4.0/ This article is distributed exclusively by Cold Spring Harbor Laboratory Press for the first six months after the full-issue publication date (see http://genesdev.cshlp.org/site/misc/terms.xhtml). After six months, it is available under a Creative Commons License (Attribution-NonCommercial 4.0 International), as described at http://creativecommons.org/licenses/by-nc/4.0/.
spellingShingle Research Paper
Liu, Xue-Song
Haines, Jenna E.
Mehanna, Elie K.
Genet, Matthew D.
Ben-Sahra, Issam
Asara, John M.
Manning, Brendan D.
Yuan, Zhi-Min
ZBTB7A acts as a tumor suppressor through the transcriptional repression of glycolysis
title ZBTB7A acts as a tumor suppressor through the transcriptional repression of glycolysis
title_full ZBTB7A acts as a tumor suppressor through the transcriptional repression of glycolysis
title_fullStr ZBTB7A acts as a tumor suppressor through the transcriptional repression of glycolysis
title_full_unstemmed ZBTB7A acts as a tumor suppressor through the transcriptional repression of glycolysis
title_short ZBTB7A acts as a tumor suppressor through the transcriptional repression of glycolysis
title_sort zbtb7a acts as a tumor suppressor through the transcriptional repression of glycolysis
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4197949/
https://www.ncbi.nlm.nih.gov/pubmed/25184678
http://dx.doi.org/10.1101/gad.245910.114
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