N-terminal domain mediated regulation of ROrα1 inhibits invasive growth in prostate cancer

Su Chan Park, Il Geun Park, Hyunkyung Kim, Ji Min Lee

Research output: Contribution to journalArticlepeer-review

5 Citations (Scopus)

Abstract

Four members of the retinoic acid-related orphan receptor α (RORα) family (RORα1, RORα2, RORα3 and RORα4) are transcription factors that regulate several processes including circadian rhythm, lipid metabolism, cerebellar development, immune function, and cancer. Only two isoforms, RORα1 and 4, are specifically co-expressed in the murine and human. In the present study, we identified a specific N-terminal domain (NTD) of RORα1 that potentiated the downregulation of target genes involved in tumor progression and proliferation, based on results from RORα-deficient mouse embryonic fibroblasts and prostate carcinoma tissues. The hyperactivation of proliferative target genes were observed in RORα-deficient embryonic fibroblasts, and reconstitution of RORα1 inhibited this activation by a NTD dependent manner. Downregulation of RORα1 and upregulation of Wnt/β-catenin target genes were correlated in prostate cancer patients. These findings revealed the control of invasive growth by NTD-mediated RORα1 signaling, suggesting advanced approaches for the development of therapeutic drugs.

Original languageEnglish
Article number1684
JournalInternational journal of molecular sciences
Volume20
Issue number7
DOIs
Publication statusPublished - 2019 Apr 1
Externally publishedYes

Keywords

  • NTD
  • Prostate cancer
  • RORα1
  • Wnt/β-catenin pathway

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

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