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CCN2 inhibits lung cancer metastasis through promoting DAPK-dependent anoikis and inducing EGFR degradation.
- Source :
-
Cell Death & Differentiation . Mar2013, Vol. 20 Issue 3, p443-455. 13p. 1 Black and White Photograph, 1 Diagram, 5 Graphs. - Publication Year :
- 2013
-
Abstract
- CCN family protein 2 (CCN2), also known as connective tissue growth factor, is a secreting protein that modulates multiple cellular events. We previously demonstrated the metastasis-suppressive effect of CCN2 in lung cancer cells. In this study, we investigate the role of CCN2 in anoikis, a form of programmed cell death that is critical in suppressing cancer metastasis. CCN2 binds to the epidermal growth factor receptor (EGFR) and triggers ubiquitination by inhibiting the formation of the β-pix/Cbl complex, resulting in the degradation of EGFR. Binding of CCN2 to EGFR suppresses the phosphorylation of c-Src and extracellular signal-regulated kinase but increases the expression of death-associated protein kinase, which leads to anoikis. Overall, our findings provide evidence validating the use of CCN2 as an anti-metastatic therapy in lung cancer patients, and prospect a potential therapeutic synergy between CCN2 and the anti-EGFR antibody for the treatment of lung cancer. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 13509047
- Volume :
- 20
- Issue :
- 3
- Database :
- Academic Search Index
- Journal :
- Cell Death & Differentiation
- Publication Type :
- Academic Journal
- Accession number :
- 85387123
- Full Text :
- https://doi.org/10.1038/cdd.2012.136