Using Micro-Western Array (MWA), a high-throughput Western blotting platform, and 434 antibodies targeting epigenetic regulation, we identified expression of 144 proteins significantly changes during the acini morphogenesis (a differentiation procedure) of prostate epithelial cells in 3D culture. ACTL6a, encoding an SWI/SNF subunit linked to stem cell and progenitor cell function, decreases most during the prostate cell differentiation, suggesting that it may be a novel oncogene in PCa. Tissue array reveals that PCa patients with high ACTL6a expression have worse survival rate. Knockdown of ACTL6a suppresses migration and invasion of PCa cells as determined by transwell assay, inhibits metastasis of prostate tumors in orthotopic model in nude mice, as well as reduces ALDH+ PCa cancer stem cells population. MWA analysis indicates that knockdown of ACTL6a reduces YAP and proteins in Hippo pathway, CD44, Sox2, Nanog, KLF4, HDAC1, HDAC3, and MMPs. Overexpression of YAP rescues the suppressive effect of ACTL6a on cancer metastasis. Our finding suggests that ACTL6a promotes metastasis and predicts poor prognosis of prostate cancer via regulation of YAP-Hippo pathway and cancer stemness.
