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The tumor suppressor adenomatous polyposis coli regulates T lymphocyte migration

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.
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https://hal-pasteur.archives-ouvertes.fr/pasteur-03681845
Contributor : FLORENCE JEANNOT Connect in order to contact the contributor
Submitted on : Monday, May 30, 2022 - 3:38:40 PM
Last modification on : Friday, August 5, 2022 - 12:03:12 PM
Long-term archiving on: : Wednesday, August 31, 2022 - 6:58:17 PM

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The tumor suppressor adenomato...
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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⟩

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