Regulation of tamoxifen sensitivity by the PLAC8/MAPK pathway axis is antagonized by curcumin-induced protein stability change

J Mol Med (Berl). 2021 Jun;99(6):845-858. doi: 10.1007/s00109-021-02047-5. Epub 2021 Feb 21.

Abstract

Tamoxifen resistance remains the major obstacle to the estrogen receptor positive breast cancer endocrine therapy. Placenta-specific 8 (PLAC8) has been implicated in epithelial-mesenchymal transition and tumorigenesis. However, the molecular mechanisms underlying PLAC8 function in the context of tamoxifen resistance are unclear. Curcumin has attracted considerable attention in the last decades. It is isolated from Curcuma longa and has beneficial effects in cancer therapy. We studied this property by using MCF-7 and tamoxifen-resistant breast cancer cells (MCF-7/TAM) cell lines. PLAC8 can regulate MCF-7/TAM cell drug sensitivity through the MAPK/ERK pathway and shows the potential effects of curcumin or as a possible druggable target against tamoxifen failure.

Keywords: Breast cancer,; Curcumin,; MAPK/ERK pathway,; PLAC8,; Tamoxifen resistance,; Ubiquitination.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Breast Neoplasms / metabolism
  • Cell Line, Tumor
  • Cell Movement
  • Curcumin / pharmacology*
  • Dose-Response Relationship, Drug
  • Drug Resistance, Neoplasm / genetics
  • Female
  • Gene Expression
  • Humans
  • Immunohistochemistry
  • Mice
  • Mitogen-Activated Protein Kinases / metabolism*
  • Models, Biological
  • Protein Binding
  • Protein Stability
  • Proteins / genetics
  • Proteins / metabolism*
  • Signal Transduction / drug effects*
  • Tamoxifen / pharmacology*
  • Ubiquitination

Substances

  • PLAC8 protein, human
  • Proteins
  • Tamoxifen
  • Mitogen-Activated Protein Kinases
  • Curcumin