Knockdown of YAP/TAZ sensitizes tamoxifen-resistant MCF7 breast cancer cells

Biochem Biophys Res Commun. 2022 Apr 23:601:73-78. doi: 10.1016/j.bbrc.2022.02.083. Epub 2022 Feb 23.

Abstract

Although endocrine therapy with tamoxifen has improved survival in breast cancer patients, resistance to this therapy remains one of the major causes of breast cancer mortality. In the present study, we found that the expression level of YAP/TAZ in tamoxifen-resistant MCF7 (MCF7-TR) breast cancer cells was significantly increased compared with that in MCF7 cells. Knockdown of YAP/TAZ with siRNA sensitized MCF7-TR cells to tamoxifen. Furthermore, siRNA targeting PSAT1, a downstream effector of YAP/TAZ, enhanced sensitivity to tamoxifen in MCF7-TR cells. Additionally, mTORC1 activity and survivin expression were significantly decreased during cell death induced by combination treatment with YAP/TAZ or PSAT1 siRNA and tamoxifen. In conclusion, targeting the YAP/TAZ-PSAT1 axis could sensitize tamoxifen-resistant MCF7 breast cancer cells by modulating the mTORC1-survivin axis.

Keywords: Breast cancer; Estrogen receptor; PSAT1; Tamoxifen resistance; YAP/TAZ.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Breast Neoplasms* / drug therapy
  • Breast Neoplasms* / genetics
  • Breast Neoplasms* / metabolism
  • Cell Line, Tumor
  • Drug Resistance, Neoplasm
  • Female
  • Humans
  • MCF-7 Cells
  • Mechanistic Target of Rapamycin Complex 1
  • RNA, Small Interfering
  • Survivin / genetics
  • Tamoxifen* / pharmacology
  • Transcriptional Coactivator with PDZ-Binding Motif Proteins* / metabolism
  • YAP-Signaling Proteins* / metabolism

Substances

  • RNA, Small Interfering
  • Survivin
  • Transcriptional Coactivator with PDZ-Binding Motif Proteins
  • YAP-Signaling Proteins
  • Tamoxifen
  • Mechanistic Target of Rapamycin Complex 1