GALNT12 suppresses the bone-specific prostate cancer metastasis by activating BMP pathway via the O-glycosylation of BMPR1A

Bone metastasis caused the majority death of prostate cancer (PCa) but the mechanism remains poorly understood.In this present study, we show that polypeptide N-acetylgalactosaminyltransferase 12 (GALNT12) suppresses bone-specific metastasis of PCa.GALNT12 suppresses proliferation, migration, invasion and cell division ability of PCa cells by activating the BMP pathway.Mechanistic investigations showed that GALNT12 augments the O-glycosylation of BMPR1A then actives the BMP pathway.Activated BMP signaling inhibits the expression of integrin αVβ3 to reduce the bone-specific seeding of PCa cells.Furthermore, activated BMP signaling remolds the immune microenvironment by suppressing the STAT3 pathway.Our results of this study illustrate the role and mechanism of GALNT12 in the process of bone metastasis of PCa and identify GALNT12 as a potential therapeutic target for metastatic PCa.