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CIP2A mediates fibronectin-induced bladder cancer cell proliferation by stabilizing β-catenin
- Source :
- Journal of Experimental & Clinical Cancer Research, Vol 36, Iss 1, Pp 1-12 (2017)
- Publication Year :
- 2017
- Publisher :
- BMC, 2017.
-
Abstract
- Abstract Background Fibronectin (FN) is associated with tumorigenesis and progression in bladder cancer, however, the underlying mechanisms causing this remain largely unknown. Furthermore, cancerous inhibitor of protein phosphatase 2A (CIP2A) has been shown to play important regulatory roles in cancer proliferation. Here, we investigated whether FN regulates CIP2A expression to promote bladder cancer cell proliferation. Methods The correlations of stromal FN with CIP2A and proliferating cell nuclear antigen (PCNA) expression were analyzed in a cohort bladder cancer patients. The roles of FN and CIP2A in regulating bladder cancer cell proliferation were evaluated in cell and animal models. Cycloheximide treatment was used to determine the effects of CIP2A on β-catenin stabilization. The CIP2A-β-catenin interaction was confirmed by immunofluorescence staining and co-immunoprcipitation. Results In this study, we found that stromal FN expression correlated positively with the levels of CIP2A and PCNA in bladder cancer tissues. Meanwhile, in human bladder cancer cell lines (T24 and J82), exogenous FN significantly promoted cell proliferation, however, CIP2A depletion inhibited this process. Furthermore, the interaction between CIP2A and β-catenin enhanced the stabilization of β-catenin, which was involved in FN-induced cell proliferation. In vivo, CIP2A depletion repressed FN-accelerated subcutaneous xenograft growth rates. Conclusions These data reveal that CIP2A is a crucial mediator of FN-induced bladder cancer cell proliferation via enhancing the stabilization of β-catenin. Promisingly, FN and CIP2A could serve as potential therapeutic targets for bladder cancer treatment.
Details
- Language :
- English
- ISSN :
- 17569966
- Volume :
- 36
- Issue :
- 1
- Database :
- Directory of Open Access Journals
- Journal :
- Journal of Experimental & Clinical Cancer Research
- Publication Type :
- Academic Journal
- Accession number :
- edsdoj.b5a1880696472b991a82945cbc5dcd
- Document Type :
- article
- Full Text :
- https://doi.org/10.1186/s13046-017-0539-8