Verteporfin inhibits YAP-induced bladder cancer cell growth and invasion via Hippo signaling pathway

Int J Med Sci. 2018 Apr 3;15(6):645-652. doi: 10.7150/ijms.23460. eCollection 2018.

Abstract

The highly conserved Hippo signaling pathway is one of the most important pathways involved in tumorigenesis and progress. Previous studies show that YAP, the transcriptional coactivator of Hippo pathway, is expressed highly in many clinical bladder cancer tissues and plays crucial role on bladder cancer progress. To find the YAP-specific target drug and its molecular mechanism in bladder cancer, we apply Verteporfin (VP), a YAP specific inhibitor to function as anti-bladder cancer drug and discover that VP is able to inhibit bladder cancer cell growth and invasion in a dosage dependent manner. Moreover, we demonstrate that VP may inhibit bladder cancer cell growth and invasion via repressing target genes' expression of the Hippo signaling pathway. In further study, we provide evidence that VP is able to inhibit excessive YAP induced bladder cancer cell growth and invasion. To address the repressive function of VP against YAP in bladder cancer, we check the target genes' expression and find VP can dramatically repress YAP overexpression induced Hippo pathway target genes' expression. Taken together, we discover that VP inhibits YAP-induced bladder cancer cell growth and invasion via repressing the target genes' expression of Hippo signaling pathway.

Keywords: Verteporfin; YAP; bladder cancer; cell growth and invasion.

MeSH terms

  • Adaptor Proteins, Signal Transducing / antagonists & inhibitors
  • Adaptor Proteins, Signal Transducing / genetics*
  • Carcinogenesis / drug effects
  • Carcinogenesis / genetics*
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Gene Expression Regulation, Neoplastic / drug effects
  • Hippo Signaling Pathway
  • Humans
  • Neoplasm Invasiveness / pathology
  • Phosphoproteins / antagonists & inhibitors
  • Phosphoproteins / genetics*
  • Porphyrins / administration & dosage*
  • Protein Serine-Threonine Kinases / genetics
  • Signal Transduction / drug effects
  • Transcription Factors
  • Urinary Bladder Neoplasms / drug therapy*
  • Urinary Bladder Neoplasms / genetics
  • Urinary Bladder Neoplasms / pathology
  • Verteporfin
  • YAP-Signaling Proteins

Substances

  • Adaptor Proteins, Signal Transducing
  • Phosphoproteins
  • Porphyrins
  • Transcription Factors
  • YAP-Signaling Proteins
  • YAP1 protein, human
  • Verteporfin
  • Protein Serine-Threonine Kinases