WWOX (Phospho-Tyr33) ELISA Kit

WW domain-containing oxidoreductase (WWOX) gene located in the common fragile site FRA16D region exhibits loss or reduction of expression in multiple types of carcinomas including bladder cancer. However, the role of WWOX in the tumorigenesis and development of bladder cancer remains elusive. In this study, WWOX overexpression construct was transfected into 5637 bladder cancer cell line in which WWOX expression was compromised. Constitutive expression of ectopic WWOX in 5637 cells suppressed cell proliferation and cell cycle progression, which was associated with downregulation of Cyclin B, D1, and E. Moreover, WWOX overexpression promoted apoptosis in 5637 cells and resulted in upregulation of Bax, downregulation of Bcl-2, and elevated levels of cleaved caspase-3 and cleaved PARP, indicating activation of the intrinsic apoptosis pathway. Furthermore, WWOX overexpression suppressed tumorigenicity of 5637 cells and promoted apoptosis in the xenograft tumors as demonstrated in a xenograft mouse model. In summary, our data indicate that WWOX plays a critical role in the regulation of proliferation, cell cycle, apoptosis, and tumorigenesis of bladder cancer cells, suggesting that WWOX may have potential clinical implications in bladder cancer therapy.

Loss of WW domain-containing oxidoreductase (Wwox) expression has been observed in breast cancer (BC). However, its regulatory effects are largely unknown, especially in triple-negative breast cancer (TNBC). Herein, gene expression profiling revealed that JAK/STAT3 pathway was one of the most differentially modulated pathways in basal-like BC cells. The lower expression of Wwox was significantly correlated with high activation of STAT3 in basal-like cells and TNBC tissues. Overexpression of Wwox markedly inhibited proliferation and metastasis of BC cells by suppressing STAT3 activation, which is to interact with JAK2 to inhibit JAK2 and STAT3 phosphorylation. Furthermore, Wwox limited STAT3 binding to the interleukin-6 promoter, repressing expression of the IL-6 cytokine. Altogether, our data established that Wwox suppresses BC cell metastasis and proliferation by JAK2/STAT3 pathway. Targeting of Wwox with STAT3 could offer a promising therapeutic strategy for TNBC.