The tumor suppressor adenomatous polyposis coli regulates T lymphocyte migration
Marta Mastrogiovanni, Pablo Vargas, Thierry Rose, Céline Cuche, Elric Esposito, Marie Juzans, Hélène Laude, Amandine Schneider, Mathilde Bernard, Sophie Goyard, Charlotte Renaudat, Marie‐Noëlle Ungeheuer, Jérôme Delon, Andrés Alcover, Vincenzo Di Bartolo
Abstract
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.