https://scholars.lib.ntu.edu.tw/handle/123456789/434926
標題: | CCN2 inhibits lung cancer metastasis through promoting DAPK-dependent anoikis and inducing EGFR degradation | 作者: | Chang C.-C. Yang M.-H. BEEN-REN LIN Chen S.-T. SZU-HUA PAN Hsiao M. Lai T.-C. SZE-KWAN LIN YUNG-MING JENG CHIA-YU CHU Chen R.-H. PAN-CHYR YANG Eugene Chin Y. Kuo M.-L. |
公開日期: | 2013 | 出版社: | Nature Publishing Group | 卷: | 20 | 期: | 3 | 起(迄)頁: | 443-455 | 來源出版物: | Cell Death and Differentiation | 摘要: | 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. |
URI: | https://www.scopus.com/inward/record.uri?eid=2-s2.0-84873709117&doi=10.1038%2fcdd.2012.136&partnerID=40&md5=c42b79cb9310d665d0ddb133621eb505 https://scholars.lib.ntu.edu.tw/handle/123456789/434926 |
ISSN: | 1350-9047 | DOI: | 10.1038/cdd.2012.136 | SDG/關鍵字: | 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 |
顯示於: | 醫學系 |
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