THE ROLE OF JUNCTIONAL ADHESION MOLECULES IN THE PATHOGENESIS AND PROGRESSION OF COLORECTAL CANCER

Somvardhan Singh Jaitawat*, Ruchi Dashora, Ravina Patidar, Dr. Siddhraj Singh Sisodia, Aditya Pant

Colorectal cancer (CRC) remains a leading cause of cancer mortality globally and is increasing in incidence in the Westernizing world. Junctional adhesion molecule (JAM) family members, JAM-A, JAM-B, JAM-C and Junctional Adhesion Molecule-like protein (JAML), have been implicated in the maintenance of epithelium integrity as well as in the regulation of cellular adhesion and modulation of immune response. Besides their role as molecular junctions, the JAM family of cell adhesion proteins participates in tumor promotion via pro-proliferative signaling acting on the tumor-promoting PI3K/AKT/mTOR axis and enhances both migratory properties, angiogenesis, and immune suppression. In CRC, their expression profile is profoundly altered, with JAM-A and JAM-B typically acting as tumor suppressors, while conversely, JAML acts as a promoter. The expressions of these lncRNAs are aberrant and correlate with tumor stage, metastasis, immune cell infiltration, and patient survival. Some JAM members are downregulated because of promoter hypermethylation, while others become more aggressive in tumours due to overexpression. These data suggest that JAMs would be applicable for biomarkers of diagnosis and prognosis, as well as a molecular target for therapy. Nevertheless, their dual role, being context-dependent, poses challenges in clinical usage. Future studies will explore the utility of molecular profiling and functional analysis of JAM in personalized medicine to improve epithelial barrier function and immunity, thereby providing a potential target for adjunctive immunotherapy.