Redox sensor CtBP mediates hypoxia-induced tumor cell migration
| Autor: | Su Yan Wang, Richard H. Goodman, David W. Piston, Qinghong Zhang, Amanda C. Nottke, Jonathan V. Rocheleau |
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| Rok vydání: | 2006 |
| Předmět: |
Motility
Biosensing Techniques Biology Cell Movement Pyruvic Acid Tumor Cells Cultured medicine Humans Neoplasm Metastasis RNA Small Interfering Hypoxia Promoter Regions Genetic Cell adhesion Gene knockdown Multidisciplinary Cadherin Biological Sciences Hypoxia (medical) Cadherins NAD Phosphoproteins CTBP2 Cell biology DNA-Binding Proteins Gene Expression Regulation Neoplastic Repressor Proteins Alcohol Oxidoreductases Cancer cell Cancer research medicine.symptom Oxidation-Reduction Intracellular |
| Zdroj: | Proceedings of the National Academy of Sciences. 103:9029-9033 |
| ISSN: | 1091-6490 0027-8424 |
| DOI: | 10.1073/pnas.0603269103 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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