Work

Redox sensor CtBP mediates hypoxia-induced tumor cell migration

Year: 2006

Type: article

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.

Source: Proceedings of the National Academy of Sciences

DOI: 10.1073/pnas.0603269103

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

Institutions: Oregon Health & Science University, Vollum Institute, Vanderbilt University

Language: English

Topic: Cancer, Hypoxia, and Metabolism

Subfield: Cancer Research

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: green

Funders: National Institutes of Health, National Cancer Institute, National Institute of Diabetes and Digestive and Kidney Diseases