EGF receptor uses SOS1 to drive constitutive activation of NFκB in cancer cells
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- Sarmishtha De
- Department of Molecular Genetics, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195
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- Josephine Kam Tai Dermawan
- Department of Molecular Genetics, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195
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- George R. Stark
- Department of Molecular Genetics, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195
書誌事項
- 公開日
- 2014-07-28
- DOI
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- 10.1073/pnas.1412390111
- 公開者
- Proceedings of the National Academy of Sciences
この論文をさがす
説明
<jats:title>Significance</jats:title> <jats:p>In normal cells, quiescent nuclear factor κB (NFκB) is activated by inflammatory stimuli. In most cancers, the abnormal constitutive activation of NFκB contributes to malignant progression and resistance to therapy. Overexpression or constitutive activation of the EGF receptor (EGFR) in many cancers contributes to their proliferation and survival. We find that the constitutive activation of NFκB in several cancer cell lines is decreased by EGFR knockdown or by the EGFR inhibitor erlotinib. We used insertional mutagenesis to find that overexpression of Son of Sevenless 1 (SOS1), a component of EGF-dependent pathways that facilitate cell growth and survival, causes erlotinib resistance and increases NFκB activation. SOS1 is required for EGF-dependent activation of NFκB but its GDP–GTP exchange activity is not, revealing a novel function for this protein.</jats:p>
収録刊行物
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- Proceedings of the National Academy of Sciences
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Proceedings of the National Academy of Sciences 111 (32), 11721-11726, 2014-07-28
Proceedings of the National Academy of Sciences
