L1CAM

Overview

L1CAM (L1 Cell Adhesion Molecule, also known as CD171) is a transmembrane glycoprotein of the immunoglobulin superfamily that mediates cell-cell and cell-matrix adhesion. It plays roles in neuronal development and cancer progression, including regulation of tumor cell migration, invasion, and resistance to chemotherapy via cell-adhesion-mediated drug resistance (CAM-DR). L1CAM is expressed aberrantly in multiple carcinoma types and has been investigated as both a prognostic biomarker and a therapeutic target.

Alterations observed in the corpus

  • Clonally enriched missense mutations (83% missense) in post-chemotherapy urothelial carcinoma (UC) tumors; GSEA on REACTOME pathways showed significant enrichment of L1CAM signaling pathway mutations in post-chemotherapy samples vs pre-chemotherapy samples (odds ratio = 1.9, FDR = 0.12) in a 32-patient matched pre/post-chemotherapy WES cohort. Proposed as a candidate driver of chemotherapy resistance through cell-adhesion-mediated drug resistance (CAM-DR). PMID:27749842

Cancer types (linked)

  • BLCA: Clonally enriched in post-chemotherapy urothelial carcinoma; the high frequency of missense (83%) mutations is consistent with potential gain-of-function alterations selected during platinum-based chemotherapy. PMID:27749842

Co-occurrence and mutual exclusivity

  • L1CAM pathway mutations co-occurred with integrin-signaling pathway enrichment (OR=2.8, FDR=0.02) in post-chemotherapy UC, suggesting coordinated cell-adhesion and integrin remodeling as a chemotherapy-resistance axis. PMID:27749842

Therapeutic relevance

  • Anti-L1CAM antibodies have demonstrated xenograft efficacy in cholangiocarcinoma, ovarian, and pancreatic ductal carcinoma models; the authors propose anti-L1CAM antibodies and Focal Adhesion Kinase (FAK) inhibitors (early-phase clinical trials) as candidate therapeutic strategies for chemotherapy-resistant urothelial carcinoma. Functional validation in UC specifically is lacking and identified as a priority. PMID:27749842

Open questions

  • Functional impact of observed L1CAM missense mutations in UC is inferred but not validated — gain-of-function studies in UC models are needed. PMID:27749842
  • Whether the CAM-DR mechanism (integrin/L1CAM-mediated resistance) is generalizable across platinum-resistant carcinomas beyond UC remains an open question. PMID:27749842

Sources

This page was processed by entity-page-writer on 2026-05-15.