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

Abstract : 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.
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Contributor : Ghislain Bidaut Connect in order to contact the contributor
Submitted on : Wednesday, May 29, 2019 - 2:52:54 PM
Last modification on : Wednesday, February 23, 2022 - 9:52:02 AM

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Sarah Garrido-Urbani, Alain Vonlaufen, Jimmy Stalin, Maria de Grandis, Patricia Ropraz, et al.. Junctional adhesion molecule C (JAM-C) dimerization aids cancer cell migration and metastasis. Biochimica et Biophysica Acta - Molecular Cell Research, 2018, 1865 (4), pp.638-649. ⟨10.1016/j.bbamcr.2018.01.008⟩. ⟨hal-02143670⟩



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