1. Stomatin-like protein 2 regulates survivin expression in non-small cell lung cancer cells through β-catenin signaling pathway
- Author
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Jeng-Ting Chen, Yu-Shien Ko, Jhy-Ming Li, Li-Fu Li, and Cheng-Ta Yang
- Subjects
Proteomics ,0301 basic medicine ,Cancer Research ,Lung Neoplasms ,genetic structures ,Survivin ,Immunology ,Apoptosis ,Article ,03 medical and health sciences ,Cellular and Molecular Neuroscience ,0302 clinical medicine ,Carcinoma, Non-Small-Cell Lung ,Cell Line, Tumor ,Humans ,Protein Interaction Maps ,RNA, Small Interfering ,lcsh:QH573-671 ,Promoter Regions, Genetic ,beta Catenin ,Cell Nucleus ,A549 cell ,Gene knockdown ,Cell growth ,Chemistry ,Akt/PKB signaling pathway ,lcsh:Cytology ,Membrane Proteins ,Blood Proteins ,Cell Biology ,equipment and supplies ,eye diseases ,Cell biology ,030104 developmental biology ,Cell culture ,030220 oncology & carcinogenesis ,RNA Interference ,sense organs ,Signal transduction ,Peptides ,Annexin A2 ,Protein Binding ,Signal Transduction - Abstract
The overexpression of stomatin-like protein-2 (SLP-2) is commonly observed in non-small cell lung cancer (NSCLC) cells. In the present study, we transfected a number of NSCLC cells with an SLP-2 shRNA-expressing vector (AdSLP2i) and examined its possible effects on cell growth and apoptosis. We found that suppression of SLP-2 expression inhibited cell growth, and that the apoptosis induced by SLP-2 suppression was correlated with decreased survivin protein expression. Moreover, the reduced survivin expression was found to be associated with reduced β-catenin nuclear localization and appeared not to be modulated through the AKT signaling pathway. By using immunoprecipitation and proteomics to analyze protein–protein interactions in A549 cells with SLP-2 overexpression, we found that annexin A2 interacted with SLP-2 and β-catenin directly. Our data further suggested that the knockdown of SLP-2 gene affected the SLP-2/Annexin A2/β-catenin cascade formation, reduced the translocation of cytoplasmic β-catenin into nucleus, and downregulated downstream target genes. The results presented in this study, together with our previous findings, suggest that SLP-2 promotes NSCLC cell proliferation by enhancing survivin expression mediated via β-catenin pathway.
- Published
- 2018