The AR/NCOA1 axis regulates prostate cancer migration by involvement of PRKD1

Area of Science:

• Oncology
• Molecular Biology
• Cell Biology

Background:

• Prostate cancer (PCa) necessitates novel therapeutic strategies.
• Investigating androgen receptor (AR)-interacting proteins is crucial for understanding PCa progression.
• Nuclear receptor coactivator 1 (NCOA1) is a potential AR-interacting protein implicated in cancer.

Purpose of the Study:

• To determine the role of NCOA1 in prostate cancer progression and metastasis.
• To investigate the effect of NCOA1 knockdown on AR-positive and AR-negative PCa cell lines.
• To elucidate the molecular mechanisms underlying NCOA1's function in PCa.

Main Methods:

• Long-term NCOA1 knockdown in PCa cell lines (MDA PCa 2b, LNCaP, PC3).
• [(3)H]-thymidine incorporation assays for proliferation assessment.
• Boyden chamber assays for migration and invasion.
• Transcriptome analysis using cDNA microarrays.
• Immunohistochemical staining of PCa patient samples.

Main Results:

• NCOA1 knockdown reduced proliferation in AR-positive PCa cells but not AR-negative cells.
• NCOA1 knockdown significantly decreased migration and invasion, irrespective of AR status.
• NCOA1 knockdown led to Protein kinase D1 (PRKD1) upregulation in AR-positive cells.
• PRKD1 inhibition reversed the reduced migration caused by NCOA1 knockdown.
• AR negatively regulates PRKD1 expression.
• NCOA1 expression was elevated in primary PCa tumors compared to normal tissue.

Conclusions:

• The AR/NCOA1 complex is associated with the regulation of PRKD1 and cellular migration in PCa.
• NCOA1 plays a significant role in PCa progression and metastasis.
• Therapeutic inhibition of NCOA1 presents a potential strategy for treating PCa.