|Title:||CCN2 inhibits lung cancer metastasis through promoting DAPK-dependent anoikis and inducing EGFR degradation||Authors:||Chang C.-C.
Eugene Chin Y.
|Issue Date:||2013||Publisher:||Nature Publishing Group||Journal Volume:||20||Journal Issue:||3||Start page/Pages:||443-455||Source:||Cell Death and Differentiation||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. ? 2013 Macmillan Publishers Limited All rights reserved.
|ISSN:||1350-9047||DOI:||10.1038/cdd.2012.136||SDG/Keyword:||Cbl protein; cetuximab; connective tissue growth factor; death associated protein kinase; epidermal growth factor receptor; mitogen activated protein kinase; p21 activated kinase interacting exchange factor; phosphatidylinositol 3 kinase; protein; protein kinase B; protein tyrosine kinase; unclassified drug; anoikis; article; cancer cell; carboxy terminal sequence; complex formation; controlled study; drug potentiation; human; human cell; lung cancer; metastasis inhibition; molecular model; priority journal; protein binding; protein degradation; protein domain; protein function; protein phosphorylation; ubiquitination
|Appears in Collections:||醫學系|
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