CIP2A is a predictor of survival and a novel therapeutic target in bladder urothelial cell carcinoma
Abstract
Cancerous inhibitor of protein phosphatase 2A (CIP2A) is a recently identified human oncoprotein that stabilizes the c-MYC protein. Herein, we aimed to investigate its expression pattern, clinical significance, and biological function in urothelial cell carcinoma (UCC) of the bladder. CIP2A expression was examined in 20 fresh bladder UCC tissues and paired adjacent normal bladder tissues by RT-PCR and Western blot. Immunohistochemistry for CIP2A was performed on additional 117 bladder UCC tissues. The clinical significance of CIP2A expression was analyzed. CIP2A downregulation was performed in bladder UCC cell line T24 with high abundance of CIP2A, and the effects of CIP2A silencing on cell proliferation, migration, invasion in vitro, and tumor growth in vivo were evaluated. We found that CIP2A expression was upregulated in bladder UCC tissues relative to adjacent normal bladder tissues. Clinicopathological analysis showed that CIP2A expression was significantly associated with tumor stage (P = 0.004), histological grade (P = 0.007), and lymph node status (P = 0.001). The Kaplan-Meier survival curves revealed that CIP2A expression was associated with poor prognosis in bladder UCC patients (log-rank value = 14.704, P < 0.001). CIP2A expression was an independent prognostic marker of overall patient survival in a multivariate analysis (P = 0.015). Knockdown of the CIP2A expression reduced cell proliferation, anchorage-independent growth, migration, invasion, and tumor growth in xenograft model mice. Our findings suggest that CIP2A is an independent predictor of poor prognosis of bladder UCC patients, and inhibition of its expression might be of therapeutic significance.
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Targeting CIP2A binding to B56 could constitute a first structure-based strategy for therapeutic inhibition of CIP2A protein stability and activity.
“As functional consequences of high CIP2A protein expression on tumorigenesis are very well established in numerous recent studies [10,14 -18], it is conceivable that targeting of CIP2A binding to B56 could constitute a first structure-based strategy for therapeutic inhibition of CIP2A protein stability and activity.”
From Oncoprotein CIP2A is stabilized via interaction with tumor suppressor PP2A/B56 (2017) · cites this paper as [17]
The therapeutic effect of inhibition of CIP2A protein expression in tumor growth has been validated by numerous studies.
“The therapeutic effect of inhibition of CIP2A protein expression in tumor growth has been recently validated by numerous studies [10,14 -18].”
From Oncoprotein CIP2A is stabilized via interaction with tumor suppressor PP2A/B56 (2017) · cites this paper as [17]
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References 45 · Cited by 34
- Authors
- Xue, Y., Wu, G., Wang, X., Zou, X., Zhang, G., Xiao, R., Yuan, Y., Long, D., Yang, J., Wu, Y., Xu, H., Liu, F., & Liu, M.
- Affiliations
- Gannan Medical University (CN)
- Corresponding author
- Zou, Xiaofeng
- Venue
- Medical Oncology
- Published
- 2012-12-30
- Volume
- 30
- Issue
- 1
- Pages
- 406-406
- ISSN
- 1357-0560 (ISSN-L)
- 1559-131X
- OpenAlex
- W2005488000
- Cited by
- 34
- References
- 45
- Citations by year
- 2025: 1 · 2023: 2 · 2021: 2 · 2020: 1 · 2019: 2 · 2018: 2 · 2017: 4 · 2016: 5 · 2015: 6 · 2014: 4 · 2013: 5
- FWCI
- 4.88
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Medical Oncology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Gannan Medical University
- Topics
- Health Sciences › Medicine › Surgery › Bladder and Urothelial Cancer Treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer-related molecular mechanisms research
- Health Sciences › Medicine › Pathology and Forensic Medicine › Cancer Mechanisms and Therapy
- Keywords
- CIP2A, bladder urothelial carcinoma, oncoprotein, prognostic factors, patient survival, tumor cell proliferation, cell migration and invasion, therapeutic target, gene knockdown
- MeSH terms
- Adult, Aged, Animals, Autoantigens, Urinary Bladder Neoplasms, Carcinoma, Transitional Cell, Female, Humans, Immunohistochemistry, Male, Membrane Proteins, Mice, Inbred BALB C, Middle Aged, Neoplasm Staging, Prognosis, Biomarkers, Tumor, Blotting, Western, Reverse Transcriptase Polymerase Chain Reaction, Xenograft Model Antitumor Assays, Intracellular Signaling Peptides and Proteins, Mice, Kaplan-Meier Estimate, Neoplasm Grading
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