Curcumin reversed chronic tobacco smoke exposure induced urocystic EMT and acquisition of cancer stem cells properties via Wnt/β-catenin

Tobacco smoke (TS) is the most important single risk factor for bladder cancer. Epithelial-mesenchymal transition (EMT) is a transdifferentiation process, involved in the initiation of TS-related cancer. Cancer stem cells (CSCs) have an essential role in the progression of many tumors including TS-related cancer. However, the molecular mechanisms of TS exposure induced urocystic EMT and acquisition of CSCs properties remains undefined. Wnt/beta-catenin pathway is critical for EMT and the maintenance of CSCs. The aim of our present study was to investigate the role of Wnt/beta-catenin pathway in chronic TS exposure induced urocystic EMT, stemness acquisition and the preventive effect of curcumin. Long time TS exposure induced EMT changes and the levels of CSCs' markers were significant upregulated. Furthermore, we demonstrated that Wnt/beta-catenin pathway modulated TS-triggered EMT and stemness, as evidenced by the findings that TS elevated Wnt/beta-catenin activation, and that TS-mediated EMT and stemness were attenuated by Wnt/beta-catenin inhibition. Treatment of curcumin reversed TS-elicited activation of Wnt/beta-catenin, EMT and CSCs properties. Collectively, these data indicated the regulatory role of Wnt/beta-catenin in TS-triggered urocystic EMT, acquisition of CSCs properties and the chemopreventive effect of curcumin.