Junctional adhesion molecule A and Sialic acid (tumor cell surface) (JAM-A and Sialic acid)

Junctional adhesion molecule A (JAM-A) is a cell-surface adhesion molecule of the immunoglobulin superfamily, concentrated at intercellular junctions in epithelial and endothelial cells but expressed in various tumor types. Sialic acids are a family of nine-carbon acidic monosaccharides present as terminal residues on surface glycans, frequently upregulated or aberrantly structured in many tumors. Both JAM-A and sialic acid serve as co-receptors for oncolytic viruses such as reovirus, with sialic acid engagement facilitating subsequent high-affinity JAM-A binding and resultant viral entry into tumor cells[1][5][8]. Beyond viral infection, tumor cell surface sialylation is an established mechanism of immune escape and is associated with cancer progression, metastasis, and resistance to immune effector mechanisms[3][4][6][7]. Targeting these molecules or their glycans is a promising strategy in cancer immunotherapy and oncolytic virotherapy, but presents challenges due to the presence of these molecules in normal tissues and their roles in basic physiological processes.

Other names

JAM-A (for Junctional adhesion molecule A)F11 receptor (F11R)Sialic acidSA (short for sialic acid)Neu5AcNeu5Gc

Inhibition of sialylation disrupts tumor cell immune evasion, enhances phagocytosis by macrophages[3][6]; Oncolytic viruses (reovirus) exploit JAM-A and sialic acid attachment for tumor-selective killing[1][5][8]; Blockade of JAM-A can affect tumor cell-cell adhesion and metastasis (preclinical models); Sialyltransferase inhibition reduces tumor cell surface sialic acid, increasing susceptibility to immune attack[3]