Redox sensor CtBP mediates hypoxia-induced tumor cell migration

Qinghong Zhang; Su Yan Wang; Amanda C. Nottke; Jonathan V. Rocheleau; David W. Piston; Richard H. Goodman

doi:10.1073/pnas.0603269103

Redox sensor CtBP mediates hypoxia-induced tumor cell migration

Qinghong Zhang, Su Yan Wang, Amanda C. Nottke, Jonathan V. Rocheleau, David W. Piston, Richard H. Goodman

Research output: Contribution to journal › Article › peer-review

155 Scopus citations

Abstract

The rapid growth and poor vascularization of solid tumors expose cancer cells to hypoxia, which promotes the metastatic phenotype by reducing intercellular adhesion and increasing cell motility and invasiveness. In this study, we found that hypoxia increased free NADH levels in cancer cells, promoting CtBP recruitment to the E-cadherin promoter. This effect was blocked by pyruvate, which prevents the NADH increase. Furthermore, hypoxia repressed E-cadherin gene expression and increased tumor cell migration, effects that were blocked by CtBP knockdown. We propose that CtBP senses levels of free NADH to control expression of cell adhesion genes, thereby promoting tumor cell migration under hypoxic stress.

Original language	English
Pages (from-to)	9029-9033
Number of pages	5
Journal	Proceedings of the National Academy of Sciences of the United States of America
Volume	103
Issue number	24
DOIs	https://doi.org/10.1073/pnas.0603269103
State	Published - Jun 13 2006

Keywords

Adhesion
E-cadherin
HIF1α
Metastasis
NADH

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title = "Redox sensor CtBP mediates hypoxia-induced tumor cell migration",

abstract = "The rapid growth and poor vascularization of solid tumors expose cancer cells to hypoxia, which promotes the metastatic phenotype by reducing intercellular adhesion and increasing cell motility and invasiveness. In this study, we found that hypoxia increased free NADH levels in cancer cells, promoting CtBP recruitment to the E-cadherin promoter. This effect was blocked by pyruvate, which prevents the NADH increase. Furthermore, hypoxia repressed E-cadherin gene expression and increased tumor cell migration, effects that were blocked by CtBP knockdown. We propose that CtBP senses levels of free NADH to control expression of cell adhesion genes, thereby promoting tumor cell migration under hypoxic stress.",

keywords = "Adhesion, E-cadherin, HIF1α, Metastasis, NADH",

author = "Qinghong Zhang and Wang, {Su Yan} and Nottke, {Amanda C.} and Rocheleau, {Jonathan V.} and Piston, {David W.} and Goodman, {Richard H.}",

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T1 - Redox sensor CtBP mediates hypoxia-induced tumor cell migration

AU - Zhang, Qinghong

AU - Wang, Su Yan

AU - Nottke, Amanda C.

AU - Rocheleau, Jonathan V.

AU - Piston, David W.

AU - Goodman, Richard H.

PY - 2006/6/13

Y1 - 2006/6/13

N2 - The rapid growth and poor vascularization of solid tumors expose cancer cells to hypoxia, which promotes the metastatic phenotype by reducing intercellular adhesion and increasing cell motility and invasiveness. In this study, we found that hypoxia increased free NADH levels in cancer cells, promoting CtBP recruitment to the E-cadherin promoter. This effect was blocked by pyruvate, which prevents the NADH increase. Furthermore, hypoxia repressed E-cadherin gene expression and increased tumor cell migration, effects that were blocked by CtBP knockdown. We propose that CtBP senses levels of free NADH to control expression of cell adhesion genes, thereby promoting tumor cell migration under hypoxic stress.

AB - The rapid growth and poor vascularization of solid tumors expose cancer cells to hypoxia, which promotes the metastatic phenotype by reducing intercellular adhesion and increasing cell motility and invasiveness. In this study, we found that hypoxia increased free NADH levels in cancer cells, promoting CtBP recruitment to the E-cadherin promoter. This effect was blocked by pyruvate, which prevents the NADH increase. Furthermore, hypoxia repressed E-cadherin gene expression and increased tumor cell migration, effects that were blocked by CtBP knockdown. We propose that CtBP senses levels of free NADH to control expression of cell adhesion genes, thereby promoting tumor cell migration under hypoxic stress.

KW - Adhesion

KW - E-cadherin

KW - HIF1α

KW - Metastasis

KW - NADH

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JF - Proceedings of the National Academy of Sciences of the United States of America

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Redox sensor CtBP mediates hypoxia-induced tumor cell migration

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