The matricellular protein CCN1 suppresses lung cancer cell growth by inducing senescence via the p53/p21 pathway.

Autor: Jim Leu SJ; Department of Biotechnology and Laboratory Science in Medicine, National Yang-Ming University, Taipei, 112, Taiwan. sjleu@ym.edu.tw, Sung JS, Chen MY, Chen CW, Cheng JY, Wang TY, Wang JJ
Jazyk: angličtina
Zdroj: Journal of cellular biochemistry [J Cell Biochem] 2013 Sep; Vol. 114 (9), pp. 2082-93.
DOI: 10.1002/jcb.24557
Abstrakt: CCN1, a secreted matrix-associated molecule, is involved in multiple cellular processes. Previous studies have indicated that expression of CCN1 correlates inversely with the aggressiveness of non-small-cell lung carcinoma (NSCLC); however, the underlying mechanisms remain elusive. Using three NSCLC cell line systems, here we show that long-term treatment of cells with the recombinant CCN1 protein led to a permanent cell cycle arrest in G1 phase; cells remained viable as judged by apoptotic assays. CCN1-treated NSCLC cells acquired a phenotype characteristic of senescent cells, including an enlarged and flattened cell shape and expression of the senescence-associated β-galactosidase. Immunoblot analysis showed that addition of CCN1 increased the abundance of hypo-phosphorylated Rb, as well as accumulation of p53 and p21. Silencing the expression of p53 or p21 by lentivirus-mediated shRNA production in cells blocked the CCN1-induced senescence. Furthermore, a CCN1 mutant defective for binding integrin α6β1 and co-receptor heparan sulfate proteoglycans was incapable of senescence induction. Our finding that direct addition of CCN1 induces senescence in NSCLC cells provides a potential novel strategy for therapeutic intervention of lung cancers.
(Copyright © 2013 Wiley Periodicals, Inc.)
Databáze: MEDLINE
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