Abstract
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/β-catenin pathway is critical for EMT and the maintenance of CSCs. The aim of our present study was to investigate the role of Wnt/β-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/β-catenin pathway modulated TS-triggered EMT and stemness, as evidenced by the findings that TS elevated Wnt/β-catenin activation, and that TS-mediated EMT and stemness were attenuated by Wnt/β-catenin inhibition. Treatment of curcumin reversed TS-elicited activation of Wnt/β-catenin, EMT and CSCs properties. Collectively, these data indicated the regulatory role of Wnt/β-catenin in TS-triggered urocystic EMT, acquisition of CSCs properties and the chemopreventive effect of curcumin.
Highlights
Bladder cancer is the ninth most common malignancy, with an estimated 429 793 new diagnosed cases and 165 084 deaths every year worldwide.[1,2] In China, bladder cancer is the first leading causes of cancer-related death among urinary malignancies.[3]
As above results revealed that cigarette smoke extract (CSE)-induced epithelial–mesenchymal transition (EMT) and acquisition of cancer stem cells (CSCs)-like properties were associated with activation of Wnt/βcatenin in CSE-transformed SV-HUC-1 cells, we further explored the role of Wnt/β-catenin pathway in this process
We evaluate whether tobacco smoke (TS)-elicited bladder EMT alterations and the CSCs characteristics are associated with changes in Wnt/β-catenin activation, the expression levels of p-GSK3β, GSK3β, p-β-catenin, β-catenin, c-Myc and cyclin D1 were measured
Summary
Bladder cancer is the ninth most common malignancy, with an estimated 429 793 new diagnosed cases and 165 084 deaths every year worldwide.[1,2] In China, bladder cancer is the first leading causes of cancer-related death among urinary malignancies.[3]. TS is strongly associated with the occurrence and development of bladder cancer.[3,4] It is reported that TS is the most important single risk factor for bladder cancer with 40–60% causally related.[4] Smokers have an estimated fourfold higher risk of bladder cancer than nonsmokers.[5] Accumulating evidence suggested that epithelial–mesenchymal transition (EMT) and the acquisition of cancer stem cells (CSCs) properties is an important underlying mechanisms for initiation, invasion and metastasis of cancer. Cell Death and Disease catenin signaling pathway is an important inducer of EMT and critical for the maintenance of CSCs. Upon activation by specific ligands, β-catenin is released from the membrane and promotes transcription of genes involved in mesenchymal phenotype induction and the maintenance of CSCs.[21] the role of Wnt/β-catenin in the long time TS exposure induced urocystic EMTand acquisition of CSCs properties still has not been defined
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