-Review-

Multiple Functions of Cell Adhesion Molecule 1 (CADM1) and Its Role in the Pathogenesis of Cancer and Other Diseases

Yoshinori Murakami¹, Yutaka Kasai¹, Tomoko Masuda¹, Hiromi Ichihara¹ and Takeshi Ito²

¹Department of Molecular Biology, Institute for Advanced Medical Sciences, Nippon Medical School, Tokyo, Japan
²Department of Internal Medicine, Section of Medical Oncology, Yale School of Medicine, New Haven, USA

Cell adhesion molecule 1 (CADM1) is an immunoglobulin superfamily cell adhesion molecule that was first identified as a tumor suppressor in non-small cell lung cancer because of its role in suppressing tumor formation in nude mice. CADM1 forms a homophilic dimer on the cell membrane and associates with actin-binding proteins (4.1s) and scaffold proteins (MAGuKs), which contain PDZ motifs. It forms a ternary protein complex involved in cell adhesion and the formation of epithelium-like structure. While CADM1 is expressed in epithelium, neuronal tissue, and testes, CADM1 expression is absent in many cancers of epithelial origin, including cancers of the lung, esophagus, stomach, liver, pancreas, breast, and prostate. In addition to its tumor-suppressive activity in epithelial cell adhesion, CADM1 acts as a tumor antigen, recognized by activated NK cells and CD8+ T cells through heterophilic interaction with CRTAM, thereby serving as a tumor suppressor in two ways. In contrast, CADM1 is overexpressed in adult T-cell leukemia/lymphoma (ATL) cells, making it a specific diagnostic marker of ATL on FACS analysis. CADM1 is also highly expressed in small cell lung cancer (SCLC) and other neuroendocrine tumors, and promotes metastasis, suggesting its potential as a target for diagnosis and treatment of SCLC. CADM1 also has a role in synapse formation and spermatogenesis, and deficient or abnormal CADM1 is linked to disorders such as male infertility in mice and autism spectrum disorder. Here, we summarize the multiple functions of CADM1 and its involvement in cancer and other diseases, focusing on disorders of aberrant cell adhesion.

J Nippon Med Sch 2025; 92: 122-131

Keywords
CADM1, immunoglobulin superfamily cell adhesion molecule (IgCAM), small cell lung cancer, tumor immunity, tumor suppressor gene

Correspondence to
Yoshinori Murakami, Department of Molecular Biology, Institute for Advanced Medical Sciences, Nippon Medical School, 1-1-5 Sendagi, Bunkyo-ku, Tokyo 113-8602, Japan
yoshinori-murakami@nms.ac.jp

Received, October 7, 2024
Accepted, December 20, 2024