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Cell Biol Toxicol ; 36(4): 287-300, 2020 08.
Article in English | MEDLINE | ID: mdl-31873818

ABSTRACT

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.


Subject(s)
Epithelial-Mesenchymal Transition/drug effects , Sulfates/pharmacology , Urinary Bladder Neoplasms/metabolism , Urinary Bladder/metabolism , Cell Line, Tumor , Cell Movement/drug effects , Cell Movement/physiology , Epithelial Cells/drug effects , Epithelial-Mesenchymal Transition/physiology , Humans , Reactive Oxygen Species/metabolism , Signal Transduction/drug effects , Signal Transduction/physiology , Urinary Bladder/pathology , Urinary Bladder Neoplasms/pathology , src-Family Kinases/metabolism , src-Family Kinases/pharmacology
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