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The tumor suppressor adenomatous polyposis coli regulates T lymphocyte migration

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Mastrogiovanni, Marta | Vargas, Pablo | Rose, Thierry | Cuche, Céline | Esposito, Elric | Juzans, Marie | Laude, Hélène | Schneider, Amandine | Bernard, Mathilde | Goyard, Sophie | Renaudat, Charlotte | Ungeheuer, Marie-Noëlle | Delon, Jérôme | Alcover, Andrés | Di Bartolo, Vincenzo

Edité par CCSD ; American Association for the Advancement of Science (AAAS) -

International audience. Adenomatous polyposis coli (APC) is a tumor suppressor whose mutations underlie familial adenomatous polyposis (FAP) and colorectal cancer. Although its role in intestinal epithelial cells is well characterized, APC importance in T cell biology is ill defined. APC regulates cytoskeleton organization, cell polarity, and migration in various cell types. Here, we address whether APC plays a role in T lymphocyte migration. Using a series of cell biology tools, we unveiled that T cells from FAP patients carrying APC mutations display impaired adhesion and motility in constrained environments. We further dissected the cellular mechanisms underpinning these defects in APC-depleted CEM T cell line that recapitulate the phenotype observed in FAP T cells. We found that APC affects T cell motility by modulating integrin-dependent adhesion and cytoskeleton reorganization. Hence, APC mutations in FAP patients not only drive intestinal neoplasms but also impair T cell migration, potentially contributing to inefficient antitumor immunity.

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