TR4 Nuclear Receptor Alters the Prostate Cancer CD133+ Stem/Progenitor Cell Invasion via Modulating the EZH2-Related...

Area of Science:

• Oncology
• Molecular Biology
• Cell Biology

Background:

• Testicular nuclear receptor 4 (TR4) is involved in metabolic disorders and tumor progression.
• Prostate cancer stem/progenitor (S/P) cells contribute to tumor aggressiveness and metastasis.

Purpose of the Study:

• To investigate the role of TR4 in prostate cancer CD133(+) S/P cell invasion.
• To elucidate the molecular mechanism by which TR4 influences prostate cancer metastasis.

Main Methods:

• Lentiviral silencing RNA was used to target TR4 in prostate cancer cells.
• In vitro and in vivo invasion assays were performed.
• Analysis of gene expression, including EZH2 and downstream targets (NOTCH1, TGFβ1, SLUG, MMP9), was conducted.
• Rescue experiments were performed by adding EZH2.

Main Results:

• Targeting TR4 significantly suppressed prostate cancer CD133(+) S/P cell invasion both in vitro and in vivo.
• TR4 was found to transcriptionally regulate the oncogene EZH2 by binding to its promoter region.
• Suppression of TR4 led to decreased expression of EZH2 and its downstream metastasis-related genes.
• Restoring EZH2 expression reversed the inhibitory effects of TR4 targeting on cell invasion.

Conclusions:

• The TR4→EZH2 signaling pathway plays a critical role in prostate cancer S/P cell invasion.
• Targeting TR4 represents a potential therapeutic strategy to combat prostate cancer metastasis.