L1 cell adhesion molecule (L1CAM), also known as neural cell adhesion molecule L1 (NCAM-L1) and CD171, is a transmembrane glycoprotein of the immunoglobulin (Ig) superfamily involved in neuronal structure and function and cell adhesion dynamics.¹

L1CAM is composed of 1257 amino acids comprising six Ig-like domains, five fibronectin type III repeats, a transmembrane region, and a highly conserved cytoplasmic tail. L1CAM is the prototype member of the L1-family of closely related neural cell adhesion molecules (CAMs). It has been shown that L1CAM is regulated by the Wnt/β-catenin signaling pathway, which is involved in maintaining cellular homeostasis, and nuclear β-catenin co-localizes with L1CAM staining in tumor sections. It has also been shown that in endometrial carcinomas, L1CAM is regulated by two distinct promoter regions and that SLUG, a zinc-finger transcription factor, is important for this regulation.¹

L1CAM plays a crucial role in neuronal migration, axon growth, and synapse formation in the developing nervous system. Dysfunction of L1CAM leads to clinically variable neurological disorders that are jointly referred to as L1 syndrome, including hydrocephalus, mental disabilities, aphasia, spastic paraplegia, and adducted thumbs.²

Although L1CAM was originally identified as a neuronal cell adhesion molecule, it has also been shown to be an essential component for disseminated cancer cells from breast, lung, kidney, and colorectal carcinomas to initiate proliferation in the brain, lung, liver, and bone. L1CAM is used to adhere and spread on the surface of blood capillaries and to activate mechanotransduction-sensitive transcription factors, which are required for the initiation of metastatic outgrowth in perivascular sites.³

L1CAM has been found in exosomes and extracellular vesicles in various contexts. For example, in the context of cancer, L1CAM-positive exosomes have been implicated in promoting cancer cell migration and invasion. Exosomes carrying L1CAM can interact with other cells, such as immune cells or endothelial cells, and potentially promote tumor progression and metastasis ^4,5.

Furthermore, in the nervous system, L1CAM is expressed in neurons and plays a role in axon guidance and neural cell adhesion. Exosomes containing L1CAM may be involved in interneuronal communication and potentially influence neural development and plasticity ^4,5.