CADM1

CADM1, or cell adhesion molecule 1, is a member of the immunoglobulin superfamily of cell adhesion molecules (IgSF CAMs) encoded by the CADM1 gene in humans. It is also known as SynCAM1 and is expressed in multiple tissues, with prominent expression in the nervous system. The protein is a single-pass transmembrane glycoprotein featuring extracellular immunoglobulin-like domains and a cytoplasmic tail that contains motifs capable of binding scaffolding proteins, enabling intracellular signaling and linkage to the cytoskeleton. Alternative splicing generates several protein isoforms.

In function, CADM1 mediates Ca2+-independent cell-cell adhesion through its extracellular region, supporting homophilic interactions (CADM1 with CADM1) as well as heterophilic interactions with other adhesion partners. In the nervous system, CADM1 contributes to synapse formation and organization, helping to arrange presynaptic and postsynaptic components and influencing synaptic maturation and function. It participates in the development and maintenance of neural circuits and has been observed to affect dendritic spine morphology in experimental systems.

CADM1 also has a recognized role in cancer biology. It acts as a tumor suppressor in several malignancies, with reduced expression associated with tumor progression and metastasis. Epigenetic silencing by promoter methylation or loss of expression has been reported in cancers such as gastric and lung cancers, among others. Restoring CADM1 expression in experimental models can reduce invasiveness and metastatic potential, highlighting its potential as a prognostic biomarker and therapeutic target.

Overall, CADM1 is a conserved cell adhesion molecule with important roles in tissue architecture, neural synapse formation, and tumor suppression, subject to regulation by transcriptional and epigenetic mechanisms.