Role of inhibitor of yes-associated protein 1 in triple-negative breast cancer with taxol-based chemoresistance

Cancer Sci. 2019 Feb;110(2):561-567. doi: 10.1111/cas.13888. Epub 2019 Jan 4.

Abstract

Triple-negative breast cancer (TNBC) is highly clinically aggressive and taxol-based chemoresistance remains a big TNBC therapeutic problem to be solved. Verteporfin, a small molecular yes-associated protein 1 (YAP1) inhibitor, is little known as an antitumor drug for TNBC. Our data showed that YAP1 expression was associated with early relapse in tissue samples of patients with TNBC taxol chemoresistance (P < .001). Verteporfin reduced migration and enhanced apoptosis or autophagy of a taxol-resistant MDA-MB-231 cell line in vitro. Knockdown of YAP1 increased epithelial-mesenchymal transition response in a taxol-resistant TNBC cell line. In an in vivo experiment, we found that verteporfin was able to shrink tumor weight and volume and decreased Ki67 expression in a taxol-resistant mouse model. Our results provide evidence that verteporfin could be a chemosensitizer for TNBC patients with taxol-based treatment.

Keywords: YAP1; chemoresistance; inhibitor; taxol; triple-negative breast cancer.

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics*
  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Animals
  • Apoptosis / drug effects
  • Apoptosis / genetics
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Cell Proliferation / genetics
  • Drug Resistance, Neoplasm / drug effects*
  • Drug Resistance, Neoplasm / genetics*
  • Epithelial-Mesenchymal Transition / drug effects
  • Epithelial-Mesenchymal Transition / genetics
  • Female
  • Gene Expression Regulation, Neoplastic / drug effects
  • Gene Expression Regulation, Neoplastic / genetics
  • Humans
  • Mice
  • Mice, Nude
  • Middle Aged
  • Paclitaxel / therapeutic use*
  • Phosphoproteins / genetics*
  • Transcription Factors
  • Triple Negative Breast Neoplasms / drug therapy*
  • Triple Negative Breast Neoplasms / genetics*
  • Xenograft Model Antitumor Assays
  • YAP-Signaling Proteins
  • Young Adult

Substances

  • Adaptor Proteins, Signal Transducing
  • Phosphoproteins
  • Transcription Factors
  • YAP-Signaling Proteins
  • YAP1 protein, human
  • Paclitaxel