L1CAM and Associated Diseases
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Backgrounds of L1CAM
L1CAM encodes for the L1 cell adhesion molecule. L1CAM is a type 1 membrane glycoprotein belonging to the immunoglobulin superfamily, consisting of 6 immunoglobulin-like domains and 5 fibronectin type III domains, with 21 potential N-glycosylation sites in the extracellular part. L1CAM was first identified in rats and was called NGF (nerve growth factor)-an inducible large external glycoprotein. L1CAM mainly exists in the nervous system and is involved in several processes, such as neuron migration, neurite bundle contraction, and synaptic plasticity, and its mutation leads to serious neurological disorders. L1CAM, a cell surface glycoprotein previously associated with the development and plasticity of the nervous system, is abnormally expressed in the vascular system of various cancers. L1CAM expression was absent from the normal human colonic epithelium but was expressed in cancer cells, and was further enriched in both matched metastasis and post-therapy relapse tumors. The intracellular domain of L1CAM mediates the connection to the actin cytoskeleton and endosomal membrane system, thereby achieving axon targeting and stabilizing the dynamics of cell surface and cell surface expression.
Fig.1 L1CAM structure. (Angiolini, 2017)
Functions of L1CAM
L1CAM is a nerve cell adhesion molecule (CAM) that is essential for the normal development of the human central nervous system. It mediates many activities important to central nervous system maturation, including neurite growth, adhesion, bunching, migration, myelination, and axon guidance. L1CAM promotes these cell activities through interactions with different CAMs, extracellular matrix molecules, and signaling receptors. It is known as a potent regulator of axon growth and branching both in vivo and in vitro and is a potential therapeutic target due to its multiple angiogenic effects in tumor-associated vascular endothelial cells. L1CAM in patients consisted of the use of a radioactively labeled antibody as an imaging tool to detect neuroblastoma, a study pointed to L1CAM as a suitable target for radioimmunotherapy of that tumor type. L1CAM has been further established as a prognostic marker, a tool for diagnostics, and most importantly a target for novel therapeutic strategies.
Fig.2 The many functions of L1CAM in cancer cells. (Raveh, 2009)
L1CAM and Associated Diseases
Different mutations of L1CAM showed that the full-length protein enhances proliferation, cell motility, and in vivo liver metastasis formation. Pathogenic variants of L1CAM are responsible for a spectrum of X-linked disorders collectively known as an L1 syndrome, including X-linked hydrocephalus with aqueductal stenosis (HSAS), mental retardation, aphasia, shuffling gait, adducted thumbs (MASA) syndrome, and isolated partial corpus callosum agenesis (CCA).
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References
- Angiolini, F.; Cavallaro, U. The pleiotropic role of L1CAM in tumor vasculature. International journal of molecular sciences. 2017, 18(2): 254.
- Raveh, S.; et al. L1 cell adhesion molecule (L1CAM) in invasive tumors. Cancer letters. 2009, 282(2): 137-145.
