期刊
SCIENCE ADVANCES
卷 8, 期 15, 页码 -出版社
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/sciadv.abl5942
关键词
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资金
- La Ligue Nationale contre le Cancer
- Equipe Labellisee Ligue
- Institut Pasteur
- INSERM
- National Research Agency (France BioImaging) [ANR-10-INBS-04]
- Investments for the Future
- European Union [665807]
- Allocation doctorale 4eme annee de these-La Ligue Contre Le Cancer
APC mutations in familial adenomatous polyposis (FAP) not only drive intestinal neoplasms but also impair T cell migration, potentially contributing to inefficient antitumor immunity.
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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