Verteporfin suppresses osteosarcoma progression by targeting the Hippo signaling pathway

Xianliang Yang1,2, Youjia Xu1, Chao Jiang2

  • 1Department of Orthopedics, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215004, P.R. China.

Oncology Letters
|August 25, 2021
PubMed

Insights

Verteporfin (VP) effectively inhibits osteosarcoma progression by downregulating YAP1 and TEAD1 expression. This targeted approach suppresses tumor cell viability, migration, and invasion, offering a promising therapeutic strategy for osteosarcoma.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Osteosarcoma is a primary bone malignancy with limited effective treatments.
  • Yes-associated protein 1 (YAP1) and TEA domain transcription factor 1 (TEAD1) are implicated in tumor progression.
  • Verteporfin (VP) is a known inhibitor of YAP1 signaling.

Purpose of the Study:

  • To investigate the inhibitory effects of Verteporfin (VP) on osteosarcoma.
  • To elucidate the underlying molecular mechanisms of VP's anticancer activity in osteosarcoma.
  • To evaluate the therapeutic potential of VP against osteosarcoma progression.

Main Methods:

  • Cell viability, cell cycle, apoptosis, migration, and invasion assays were performed.
  • Gene and protein expression levels of YAP1, TEAD1, and CYR61 were analyzed.
  • Co-immunoprecipitation identified YAP1 and TEAD1 interactions.
  • In vivo mouse xenograft models assessed tumor growth inhibition.

Main Results:

  • YAP1 and TEAD1 were highly expressed in osteosarcoma.
  • VP significantly downregulated YAP1 and TEAD1 expression in Saos-2 cells.
  • VP suppressed osteosarcoma cell viability, migration, invasion, and induced apoptosis and G1 cell cycle arrest.
  • VP inhibited tumor growth in a mouse xenograft model.
  • CYR61 overexpression partially reversed VP's inhibitory effects.

Conclusions:

  • Verteporfin (VP) effectively suppresses osteosarcoma progression by inhibiting YAP1 and TEAD1 expression.
  • VP demonstrates significant anticancer effects on osteosarcoma cells in vitro and in vivo.
  • CYR61 may play a mediating role in VP's therapeutic action against osteosarcoma.