2. Academic Validation
  3. BSA-bounded p-cresyl sulfate potentiates the malignancy of bladder carcinoma by triggering cell migration and EMT through the ROS/Src/FAK signaling pathway

BSA-bounded p-cresyl sulfate potentiates the malignancy of bladder carcinoma by triggering cell migration and EMT through the ROS/Src/FAK signaling pathway

  • Cell Biol Toxicol. 2020 Aug;36(4):287-300. doi: 10.1007/s10565-019-09509-0.
Yu-Sen Peng 1 2,  Jhih-Pu Syu 3,  Sheng-De Wang 3,  Pie-Chun Pan 3,  Hsiu-Ni Kung 4
Affiliations

Affiliations

  • 1 Division of Nephrology, Department of Internal Medicine, Far Eastern Memorial Hospital, Taipei, Taiwan.
  • 2 Department of Electrical Engineering, Yuan-Ze University, Taoyuan City, Taiwan.
  • 3 Graduate Institute of Anatomy and Cell Biology, College of Medicine, National Taiwan University, 1-1 Jen-Ai Road, 10051, Taipei, Taiwan.
  • 4 Graduate Institute of Anatomy and Cell Biology, College of Medicine, National Taiwan University, 1-1 Jen-Ai Road, 10051, Taipei, Taiwan. kunghsiuni@gmail.com.
PMID: 31873818 DOI: 10.1007/s10565-019-09509-0
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.

Keywords

BSA-bound p-cresyl sulfate; Bladder urothelioma; EMT; Focal adhesion kinase; Migration; ROS; Src.

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