TY - JOUR
T1 - N-terminal domain mediated regulation of ROrα1 inhibits invasive growth in prostate cancer
AU - Park, Su Chan
AU - Park, Il Geun
AU - Kim, Hyunkyung
AU - Lee, Ji Min
N1 - Funding Information:
Funding: This work was supported by the Basic Science Research Program (NRF-2018R1D1A1A02085592) from the National Research Foundation (NRF) grant funded by the Korean government and 2019 Research Grant from Kangwon National University.
Funding Information:
This work was supported by the Basic Science Research Program (NRF-2018R1D1A1A02085592) from the National Research Foundation (NRF) grant funded by the Korean government and 2019 Research Grant from Kangwon National University.
Publisher Copyright:
© 2019 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2019/4/1
Y1 - 2019/4/1
N2 - 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.
AB - 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.
KW - NTD
KW - Prostate cancer
KW - RORα1
KW - Wnt/β-catenin pathway
UR - http://www.scopus.com/inward/record.url?scp=85064928698&partnerID=8YFLogxK
U2 - 10.3390/ijms20071684
DO - 10.3390/ijms20071684
M3 - Article
C2 - 30987323
AN - SCOPUS:85064928698
SN - 1661-6596
VL - 20
JO - International Journal of Molecular Sciences
JF - International Journal of Molecular Sciences
IS - 7
M1 - 1684
ER -
