L1 Cell Adhesion Molecule in Cancer, a Systematic Review on Domain-Specific Functions

• Published in: International journal of molecular sciences 2019-08, Vol.20 (17), p.4180
• Main Authors: Maten, Miriam van der, Reijnen, Casper, Pijnenborg, Johanna M A, Zegers, Mirjam M
• Format: Article
• Language: English
• Subjects: Animals; Apoptosis; Ascites; Biomarkers; Breast cancer; Carrier Proteins; Cell Adhesion; Cell adhesion & migration; Cell adhesion molecules; Cell growth; Cell proliferation; Cell Transformation, Neoplastic - genetics; Cell Transformation, Neoplastic - metabolism; Chemoresistance; Esophagus; Gastric cancer; Gene expression; Humans; Melanoma; Mesenchyme; Metastases; Metastasis; Neoplasms - etiology; Neoplasms - metabolism; Neoplasms - pathology; Neural Cell Adhesion Molecule L1 - chemistry; Neural Cell Adhesion Molecule L1 - metabolism; Neuroblastoma; Non-small cell lung carcinoma; Ovarian cancer; Ovarian carcinoma; Pancreatic cancer; Phenotypes; Protein Binding; Protein Interaction Domains and Motifs; Proteins; Review; Signal Transduction; Systematic review; Tumors
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms20174180

L1 cell adhesion molecule (L1CAM) is a glycoprotein involved in cancer development and is associated with metastases and poor prognosis. Cellular processing of L1CAM results in expression of either full-length or cleaved forms of the protein. The different forms of L1CAM may localize at the plasma membrane as a transmembrane protein, or in the intra- or extracellular environment as cleaved or exosomal forms. Here, we systematically analyze available literature that directly relates to L1CAM domains and associated signaling pathways in cancer. Specifically, we chart its domain-specific functions in relation to cancer progression, and outline pre-clinical assays used to assess L1CAM. It is found that full-length L1CAM has both intracellular and extracellular targets, including interactions with integrins, and linkage with ezrin. Cellular processing leading to proteolytic cleavage and/or exosome formation results in extracellular soluble forms of L1CAM that may act through similar mechanisms as compared to full-length L1CAM, such as integrin-dependent signals, but also through distinct mechanisms. We provide an algorithm to guide a step-wise analysis on L1CAM in clinical samples, to promote interpretation of domain-specific expression. This systematic review infers that L1CAM has an important role in cancer progression that can be attributed to domain-specific forms. Most studies focus on the full-length plasma membrane L1CAM, yet knowledge on the domain-specific forms is a prerequisite for selective targeting treatment.