Linking L1CAM-mediated signaling to NF-κB activation

Trends Mol Med. 2011 Apr;17(4):178-87. doi: 10.1016/j.molmed.2010.11.005. Epub 2010 Dec 30.

Abstract

The cell adhesion molecule L1 (L1CAM) was originally identified as a neural adhesion molecule essential for neurite outgrowth and axon guidance. Many studies have now shown that L1CAM is overexpressed in human carcinomas and associated with poor prognosis. So far, L1CAM-mediated cellular signaling has been largely attributed to an association with growth factor receptors, referred to as L1CAM-'assisted' signaling. New data demonstrate that L1CAM can signal via two additional mechanisms: 'forward' signaling via regulated intramembrane proteolysis and 'reverse' signaling via the activation of the transcription factor nuclear factor (NF)-κB. Taken together, these findings lead to a new understanding of L1CAM downstream signaling that is fundamental for the development of anti-L1CAM antibody-mediated therapeutics in human tumor cells.

Publication types

  • Review

MeSH terms

  • Animals
  • Cell Adhesion
  • Cell Line, Tumor
  • Cell Nucleus / metabolism
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Interleukin-1beta / metabolism
  • MAP Kinase Signaling System
  • NF-kappa B / genetics
  • NF-kappa B / metabolism*
  • Neural Cell Adhesion Molecule L1 / genetics
  • Neural Cell Adhesion Molecule L1 / metabolism*
  • Receptor Protein-Tyrosine Kinases / genetics
  • Receptor Protein-Tyrosine Kinases / metabolism
  • Signal Transduction*
  • Transcription Factors / genetics
  • Transcription Factors / metabolism

Substances

  • Interleukin-1beta
  • NF-kappa B
  • Neural Cell Adhesion Molecule L1
  • Transcription Factors
  • Receptor Protein-Tyrosine Kinases