Junctional adhesion molecule C (JAM-C) dimerization aids cancer cell migration and metastasis.

Autor: Garrido-Urbani S; Department of Pathology and Immunology, University of Geneva, Geneva, Switzerland. Electronic address: sarah.deblon@hotmail.com., Vonlaufen A; Department of Pathology and Immunology, University of Geneva, Geneva, Switzerland., Stalin J; Department of Pathology and Immunology, University of Geneva, Geneva, Switzerland., De Grandis M; Centre de Recherche en Cancérologie de Marseille, Inserm, UMR1068, Marseille, France; Institut Paoli-Calmettes, Marseille, France; Aix-Marseille Université, Marseille, France; CNRS, UMR7258, Marseille, France., Ropraz P; Department of Pathology and Immunology, University of Geneva, Geneva, Switzerland., Jemelin S; Department of Pathology and Immunology, University of Geneva, Geneva, Switzerland., Bardin F; Centre de Recherche en Cancérologie de Marseille, Inserm, UMR1068, Marseille, France; Institut Paoli-Calmettes, Marseille, France; Aix-Marseille Université, Marseille, France; CNRS, UMR7258, Marseille, France., Scheib H; Venom Evolution Lab, School of Biological Sciences, University of Queensland, St Lucia, Queensland 4072, Australia., Aurrand-Lions M; Centre de Recherche en Cancérologie de Marseille, Inserm, UMR1068, Marseille, France; Institut Paoli-Calmettes, Marseille, France; Aix-Marseille Université, Marseille, France; CNRS, UMR7258, Marseille, France., Imhof BA; Department of Pathology and Immunology, University of Geneva, Geneva, Switzerland. Electronic address: beat.imhof@unige.ch.
Jazyk: angličtina
Zdroj: Biochimica et biophysica acta. Molecular cell research [Biochim Biophys Acta Mol Cell Res] 2018 Apr; Vol. 1865 (4), pp. 638-649. Date of Electronic Publication: 2018 Jan 31.
DOI: 10.1016/j.bbamcr.2018.01.008
Abstrakt: Most cancer deaths result from metastasis, which is the dissemination of cells from a primary tumor to distant organs. Metastasis involves changes to molecules that are essential for tumor cell adhesion to the extracellular matrix and to endothelial cells. Junctional Adhesion Molecule C (JAM-C) localizes at intercellular junctions as homodimers or more affine heterodimers with JAM-B. We previously showed that the homodimerization site (E66) in JAM-C is also involved in JAM-B binding. Here we show that neoexpression of JAM-C in a JAM-C-negative carcinoma cell line induced loss of adhesive property and pro-metastatic capacities. We also identify two critical structural sites (E66 and K68) for JAM-C/JAM-B interaction by directed mutagenesis of JAM-C and studied their implication on tumor cell behavior. JAM-C mutants did not bind to JAM-B or localize correctly to junctions. Moreover, mutated JAM-C proteins increased adhesion and reduced proliferation and migration of lung carcinoma cell lines. Carcinoma cells expressing mutant JAM-C grew slower than with JAM-C WT and were not able to establish metastatic lung nodules in mice. Overall these data demonstrate that the dimerization sites E66-K68 of JAM-C affected cell adhesion, polarization and migration and are essential for tumor cell metastasis.
(Copyright © 2018 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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