The tumor suppressor adenomatous polyposis coli regulates T lymphocyte migration

Marta Mastrogiovanni (1, 2) , Pablo Vargas (3, 4) , Thierry Rose (1) , Céline Cuche (1) , Elric Esposito (5) , Marie Juzans (1) , Hélène Laude (6) , Amandine Schneider (1) , Mathilde Bernard (3, 4) , Sophie Goyard (1) , Charlotte Renaudat (6) , Marie-Noëlle Ungeheuer (6) , Jérôme Delon (7) , Andrés Alcover (1) , Vincenzo Di Bartolo (1)

1 Biologie Cellulaire des Lymphocytes - Lymphocyte Cell Biology
2 Collège Doctoral
3 Biologie Cellulaire et Cancer
4 Institut Pierre-Gilles de Gennes pour la Microfluidique
5 UTechS PBI - BioImagerie Photonique – Photonic BioImaging
6 ICAReB - Investigation Clinique et d’Accès aux Ressources Biologiques (Plate-forme) - Clinical Investigation and Access to BioResources
7 IC UM3 (UMR 8104 / U1016) - Institut Cochin

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.

Domains: Life Sciences [q-bio]

Marta Mastrogiovanni, Pablo Vargas, Thierry Rose, Céline Cuche, Elric Esposito, et al.. The tumor suppressor adenomatous polyposis coli regulates T lymphocyte migration. Science Advances , 2022, 8 (15), pp.eabl5942. ⟨10.1126/sciadv.abl5942⟩. ⟨pasteur-03681845⟩