Oncogenic role of PinX1 in prostate cancer cells through androgen receptor dependent and independent mechanisms

J Steroid Biochem Mol Biol. 2021 Jun;210:105858. doi: 10.1016/j.jsbmb.2021.105858. Epub 2021 Feb 26.

Abstract

Coregulators play an important role in prostate cancer (PCa), modulating androgen receptor (AR) action and representing a possible cause of androgen deprivation therapy failure. Pin2-interacting protein X1 (PinX1) is a nucleolar protein described as a steroid hormone receptor coregulator in breast cancer cell lines. In this work, we studied the effect of PinX1 on AR action in PCa. Our results demonstrate that PinX1 acts as an AR coactivator, increasing its transcriptional activity and target gene expression, as well as proliferation, migration and colony formation in PCa cell lines. These effects are observed in the presence and absence of AR agonist and antagonists, suggesting a possible androgen independent pathway for PinX1. We present the first oncogenic roles described for PinX1, acting as a coactivator of the AR.

Keywords: AR; Coactivators; Coregulators; PinX1; Prostate cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Binding Sites
  • Cell Cycle Proteins / genetics
  • Cell Cycle Proteins / metabolism*
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Nucleus / metabolism
  • Cell Proliferation / genetics
  • Epithelial-Mesenchymal Transition / genetics
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Male
  • Promoter Regions, Genetic
  • Prostatic Neoplasms / genetics
  • Prostatic Neoplasms / metabolism*
  • Prostatic Neoplasms / pathology*
  • Receptors, Androgen / genetics
  • Receptors, Androgen / metabolism*
  • Tumor Stem Cell Assay
  • Tumor Suppressor Proteins / genetics
  • Tumor Suppressor Proteins / metabolism*

Substances

  • AR protein, human
  • Cell Cycle Proteins
  • PINX1 protein, human
  • Receptors, Androgen
  • Tumor Suppressor Proteins