Para-cresyl sulfate (P-CS), a major uremic toxin derived from the metabolites of tyrosine and phenylalanine through liver, existed in the blood of patients with chronic kidney disease (CKD). CKD increases the malignancy in bladder cancers; however, effects of P-CS on bladder cancers are not fully understood. P-CS is conjugated with BSA physiologically, and this study aims to investigate the effects and possible underlying mechanisms of BSA-bounded P-CS on human bladder cancer cells. With P-CS treatment, the intracellular ROS increased in bladder cancer cells. ROS then triggered epithelial-mesenchymal transition (EMT), stress fiber redistribution, and cell migration. With specific inhibitors, the key signals regulating P-CS-treated migration are Src and FAK. This study provided a clinical clue that patients with higher serum P-CS have a higher risk of malignant urothelial carcinomas, and a regulatory pathway of how P-CS regulates bladder cancer migration.

中文翻译：

---

BSA结合的对甲酚硫酸盐可通过ROS / Src / FAK信号通路触发细胞迁移和EMT来增强膀胱癌的恶性程度。

慢性肾病（CKD）患者的血液中存在对甲酚硫酸盐（P-CS），这是一种主要的尿毒症毒素，是通过肝脏酪氨酸和苯丙氨酸的代谢产物而产生的。CKD增加了膀胱癌的恶性程度；然而，P-CS对膀胱癌的作用尚不完全清楚。P-CS在生理上与BSA偶联，并且本研究旨在研究BSA结合的P-CS对人膀胱癌细胞的影响及其可能的潜在机制。通过P-CS处理，膀胱癌细胞中的细胞内ROS增加。ROS随后触发了上皮-间质转化（EMT），应力纤维重新分布和细胞迁移。使用特定的抑制剂，调节P-CS处理的迁移的关键信号是Src和FAK。