YAP overexpression promotes the epithelial-mesenchymal transition and chemoresistance in pancreatic cancer cells

Mol Med Rep. 2016 Jan;13(1):237-42. doi: 10.3892/mmr.2015.4550. Epub 2015 Nov 11.

Abstract

The expression of Yes-associated protein (YAP) has been reported to be dysregulated in pancreatic cancer. However, its contributions to tumor formation and progression remain to be elucidated. The present study demonstrated that YAP overexpression promoted the epithelial‑mesenchymal transition (EMT) in a manner associated with pancreatic cancer invasion in vitro. RNA interference‑mediated silencing of YAP attenuated cell invasion in vitro. Mechanistically, the present study demonstrated that YAP overexpression fosters pancreatic cancer progression by inducing the EMT in pancreatic cancer cells by activating the AKT cascade, which can counteract the effect of gemcitabine. These data suggested that the YAP acts synergistically to promote pancreatic cancer progression by hyperactivation of AKT signaling. The present study revealed YAP as a potential therapeutic target for pancreatic cancer and a biomarker for predicting gemcitabine treatment response.

MeSH terms

  • Adaptor Proteins, Signal Transducing / metabolism*
  • Cell Line, Tumor
  • Deoxycytidine / analogs & derivatives
  • Deoxycytidine / pharmacology
  • Disease Progression
  • Drug Resistance, Neoplasm* / drug effects
  • Enzyme Activation / drug effects
  • Epithelial-Mesenchymal Transition* / drug effects
  • Gemcitabine
  • Humans
  • Neoplasm Invasiveness
  • Pancreatic Neoplasms / enzymology
  • Pancreatic Neoplasms / pathology*
  • Phenotype
  • Phosphoproteins / metabolism*
  • Proto-Oncogene Proteins c-akt / metabolism
  • Signal Transduction / drug effects
  • Transcription Factors
  • Up-Regulation / drug effects
  • YAP-Signaling Proteins

Substances

  • Adaptor Proteins, Signal Transducing
  • Phosphoproteins
  • Transcription Factors
  • YAP-Signaling Proteins
  • YAP1 protein, human
  • Deoxycytidine
  • Proto-Oncogene Proteins c-akt
  • Gemcitabine