O-GalNAc Glycosylation Activates MBL-Mediated Complement and Coagulation Cascades to Drive Organotropic Metastasis.

ABSTRACT: Liver metastasis is prevalent among patients with neuroendocrine prostate cancer (NEPC) and other types of neuroendocrine (NE) cancers, featuring with an aggressive clinical course and a dismal prognosis. However, the cellular and molecular mechanisms underlying liver-specific metastatic tropism in NE cancers remain poorly understood. Intriguingly, it is found that NEPC liver metastatic foci are frequently associated with thrombi. NEPC cells express an aberrantly elevated level of glycosyltransferase Galnt9. Notably, the Galnt9-mediated O-GalNAc glycosylation on the cell membrane of NE cancer cells, particularly on the adhesion molecule Annexin A2, activates the mannose-binding lectin (MBL) complement signaling in the liver. This cascade stimulates platelet activation and thrombus formatio

SUBMITTER: Chen X 

PROVIDER: S-EPMC12407318 | biostudies-literature | 2025 Aug

REPOSITORIES: biostudies-literature