Mechanical Control of Cell Migration by the Metastasis Suppressor Tetraspanin CD82/KAI1

Laura Ordas (1) , Luca Costa (1) , Anthony Lozano (2) , Christopher Chevillard (3) , Alexia Calovoulos (1) , Diala Kantar (4) , Laurent Fernandez (5) , Lucie Chauvin (6) , Patrice Dosset (1) , Christine Doucet (1) , Lisa Heron-Milhavet (4) , Elena Odintsova (7) , Fedor Berditchevski (7) , Pierre-Emmanuel Milhiet (1) , Christine Bénistant (1)

1 CBS - Centre de Biochimie Structurale [Montpellier]
2 IGMM - Institut de Génétique Moléculaire de Montpellier
3 IBS - UMR 5075 - Institut de biologie structurale
4 IRCM - U1194 Inserm - UM - Institut de Recherche en Cancérologie de Montpellier
5 ARNA - Acides Nucléiques : Régulations Naturelle et Artificielle
6 IGDR - Institut de Génétique et Développement de Rennes
7 Institute of Cancer and Genomic Sciences, University of Birmingham

The plasma membrane is a key actor of cell migration. For instance, its tension controls persistent cell migration and cell surface caveolae integrity. Then, caveolae constituents such as caveolin-1 can initiate a mechanotransduction loop that involves actin- and focal adhesion-dependent control of the mechanosensor YAP to finely tune cell migration. Tetraspanin CD82 (also named KAI-1) is an integral membrane protein and a metastasis suppressor. Its expression is lost in many cancers including breast cancer. It is a strong inhibitor of cell migration by a little-known mechanism. We demonstrated here that CD82 controls persistent 2D migration of EGF-induced single cells, stress fibers and focal adhesion sizes and dynamics. Mechanistically, we found that CD82 regulates membrane tension, cell surface caveolae abundance and YAP nuclear translocation in a caveolin-1-dependent manner. Altogether, our data show that CD82 controls 2D cell migration using membrane-driven mechanics involving caveolin and the YAP pathway.

Mots clés: YAP; actin; caveolins; cell migration; focal adhesions; mechanotransduction; plasma membrane; tetraspanins

Domaines: Biophysique; Cancer

Laura Ordas, Luca Costa, Anthony Lozano, Christopher Chevillard, Alexia Calovoulos, et al.. Mechanical Control of Cell Migration by the Metastasis Suppressor Tetraspanin CD82/KAI1. Cells, 2021, 10 (6), pp.1545. ⟨10.3390/cells10061545⟩. ⟨hal-03415288⟩