Journal
CANCER LETTERS
Volume 354, Issue 2, Pages 378-389Publisher
ELSEVIER IRELAND LTD
DOI: 10.1016/j.canlet.2014.08.045
Keywords
Ribosomal protein S6 (rpS6); Non-small cell lung cancer (NSCLC); Growth; Cell cycle; Apoptosis
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Funding
- National Natural Science Foundation of China [81241068, 81372504]
- National High Technology Research and Development Program of China (863 Program) [2014AA022202]
- Chinese Postdoctoral Science Foundation [2013M542281]
- Application of Infrastructure Program from the Department of Science and Technology, Sichuan Province, China [2013JY0012]
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Ribosomal protein S6 (rpS6), a component of the small 40S ribosomal subunit, has been found to be associated with multiple physiological and pathophysiological functions. However, its effects and mechanisms in non-small cell lung cancer (NSCLC) still remain unknown. Here, we showed that expressions of total rpS6 and phosphorylation rpS6 (p-rpS6) were both significantly overexpressed in NSCLC. Further survival analysis revealed the shortened overall survival (OS) and relapse-free survival (RFS) in p-rpS6 overexpressed patients and confirmed it as an independent adverse predictor. Stable downregulation of rpS6 in lung adenocarcinoma A549 and squamous cell carcinoma H520 cell lines was then achieved by two specific small hairpin RNA (shRNA) lentiviruses separately. Subsequent experiments showed that downregulation of rpS6 dramatically inhibited cell proliferation in vitro and tumorigenicity in vivo. Moreover, loss of rpS6 promoted cells arrested in G0-G1 phase and reduced in G2-M phase, along with the expression alterations of relative proteins. However, no notable change in apoptosis was observed. Collectively, these results suggested that rpS6 is overactivated in NSCLC and its downregulation suppresses the growth of NSCLC mainly by inducing G0-G1 cell cycle arrest rather than apoptosis. (C) 2014 Elsevier Ireland Ltd. All rights reserved.
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