Opioid-binding cell adhesion molecule (OPCML) (OPCML)

Opioid-binding cell adhesion molecule (OPCML) is a glycosylphosphatidylinositol (GPI)-anchored cell surface protein belonging to the IgLON subfamily of the immunoglobulin superfamily. It acts as a potent tumor suppressor and is frequently inactivated via epigenetic silencing (promoter methylation) or allelic loss in a wide range of human cancers, most notably ovarian, breast, and lung carcinomas. Biologically, OPCML functions by interacting with the extracellular domains of several oncogenic receptor tyrosine kinases (RTKs), including HER2, EGFR, FGFR, and AXL. This interaction leads to the sequestration of these RTKs into non-lipid raft domains and promotes their endocytosis and subsequent ubiquitin-mediated degradation, thereby downregulating pro-proliferative and pro-survival signaling pathways. Therapeutically, OPCML is being explored through protein replacement strategies using recombinant OPCML (e.g., PYTX-004) to restore its tumor-suppressive function and sensitize cancer cells to existing RTK inhibitors and chemotherapy. Because it operates on the cell surface, it is a uniquely accessible tumor suppressor for pharmacological intervention compared to intracellular targets.

Other names

OBCAMOPCMIGLON1IgLON family member 1Opioid-binding protein/cell adhesion molecule

Restoration of tumor suppressor activity via protein replacement; physical sequestration and downregulation of oncogenic receptor tyrosine kinases (RTKs) such as HER2, EGFR, and AXL; potentiation of RTK inhibitors by disrupting receptor heterodimerization.