Higher expression of Annexin A2 in bladder urothelial carcinoma promotes migration and invasion.




Guo, Christina
Chaudhary, Pankaj


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Purpose:Bladder cancer is a prevalent and often aggressive malignancy, precipitating high morbidity and mortality rates in the US. The paucity of non-invasive and low-cost methods for detection necessitates investigation into improved surveillance assays for bladder urothelial carcinoma (BLCA). Annexin A2 (AnxA2) is a phospholipid-binding protein involved in malignant processes in several cancers but has yet to be studied in association with bladder carcinoma. This study aims to investigate the association of AnxA2 in BLCA and establish its role in the metastasis of bladder cancer cells.

Results:The Cancer Genome Atlas Data analysis demonstrated that AnxA2 mRNA expression was significantly increased in BLCA tumor tissue compared to normal bladder tissue. Higher AnxA2 mRNA expression was significantly associated with high pathological grades, stages, and non-papillary tumor histology and poor overall survival, progression-free survival, and disease-specific survival. Similarly, we found that AnxA2 expression was higher in bladder cancer cells derived from high-grade metastatic carcinoma than in cells derived from low-grade urothelial carcinoma. In addition, expression of AnxA2 was significantly mobilized to the surface of bladder cancer cells that were highly metastatic versus cancer cells derived from low-grade tumors. This expression was also associated with high plasmin generation and AnxA2 secretion. Downregulation of AnxA2 cells significantly inhibited proliferation, migration, and invasion in bladder cancer and decreased expression of proangiogenic growth factors and cytokines.

Conclusion: Results of this study show that higher expression of AnxA2 is involved in proliferation, migration, and invasion in bladder cancer and is associated with poor prognosis of patients with BLCA. These findings demonstrate the potential for AnxA2 as a prognostic marker and therapeutic target for BLCA.

Funding: This research was partly supported by the NIH grants CA233355 and HL125447. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH.