title: Linking L1CAM-mediated signaling to NF-κB activation.
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.
authors.affiliation: Translational Immunology, D015, German Cancer Research Center, 69120 Heidelberg, Germany.
authors.forename: Helena
authors.initials: H
authors.lastname: Kiefel
authors.forename: Marco
authors.initials: M
authors.lastname: Pfeifer
authors.forename: Sandra
authors.initials: S
authors.lastname: Bondong
authors.forename: John
authors.initials: J
authors.lastname: Hazin
authors.forename: Peter
authors.initials: P
authors.lastname: Altevogt
mesh_terms: D000818:Animals; D002448:Cell Adhesion; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D053583:Interleukin-1beta / Q000378:metabolism; D020935:MAP Kinase Signaling System; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism*; D039842:Neural Cell Adhesion Molecule L1 / Q000235:genetics / Q000378:metabolism*; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
chemical_list: D053583:Interleukin-1beta; D016328:NF-kappa B; D039842:Neural Cell Adhesion Molecule L1; D014157:Transcription Factors; D020794:Receptor Protein-Tyrosine Kinases