Abstract
L1 cell adhesion molecule (L1CAM) is aberrantly expressed in several tumor types where it is causally linked to malignancy and therapy resistance, acting also as a poor prognosis factor. Accordingly, several approaches have been developed to interfere with L1CAM function or to deliver cytotoxic agents to L1CAM-expressing tumors. Metastatic dissemination, tumor relapse and drug resistance can be fueled by a subpopulation of neoplastic cells endowed with peculiar biological properties that include self-renewal, efficient DNA repair, drug efflux machineries, quiescence, and immune evasion. These cells, known as cancer stem cells (CSC) or tumor-initiating cells, represent, therefore, an ideal target for tumor eradication. However, the molecular and functional traits of CSC have been unveiled only to a limited extent. In this context, it appears that L1CAM is expressed in the CSC compartment of certain tumors, where it plays a causal role in stemness itself and/or in biological processes intimately associated with CSC (e.g., epithelial-mesenchymal transition (EMT) and chemoresistance). This review summarizes the role of L1CAM in cancer focusing on its functional contribution to CSC pathophysiology. We also discuss the clinical usefulness of therapeutic strategies aimed at targeting L1CAM in the context of anti-CSC treatments.
Highlights
The L1 cell adhesion molecule (L1CAM, known as CD171) was described for the first time by Schachner et al in the central nervous system (CNS) [1]
L1CAM has been primarily implicated in the development and plasticity of the nervous system, where it plays a pivotal role in neuronal migration and differentiation, neurite outgrowth, axon guidance, fasciculation of axons and dendrites, myelination, and synaptogenesis [2,3,4]
The proteins involved in a functional and/or physical interaction with L1CAM belong to different classes including other Ig-cell adhesion molecules (CAMs), proteoglycans, integrins, extra cellular matrix proteins, co-receptors, cytoskeletal proteins, and Receptor Tyrosine Kinases (RTKs) such as Fibroblast Growth Factor (FGF) and Epidermal Growth Factor (EGF) receptors
Summary
The L1 cell adhesion molecule (L1CAM, known as CD171) was described for the first time by Schachner et al in the central nervous system (CNS) [1]. The L1 subfamily comprises four different members which share an analogous structural organization: Close Homolog of L1 (CHL1), Neuronal Cell Adhesion Molecule (NrCAM), Neurofascin and L1CAM itself [8]. All these proteins, in turn, belong to the Immunoglobulin superfamily of CAMs (Ig-CAMs), which owes its name to the presence of Ig-like domains in the extracellular portion of these proteins. The existence of such horseshoe-dependent structures is still controversial as some researchers attribute this conformation to a complicated mixture of other quaternary structures at a higher level of complexity rather than to a structure per se [14]
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