Biophysical Society Thematic Meeting| Aussois 2019

Biology and Physics Confront Cell-Cell Adhesion

Poster Abstracts

18-POS Board 18 THE TUMOR SUPPRESSOR ADENOMATOUS POLYPOSIS COLI AS A REGULATOR OF T CELL MOTILITY AND POLARITY Marta Mastrogiovanni 1,2 ; Céline Couche 1 ; Thierry Rose 3 ; Jérôme Delon 4 ; Andrés Alcover 1 ; Vincenzo Di Bartolo 1 ; 1 Institut Pasteur, Immunology , Paris, France Adenomatous polyposis coli (APC) is a tumor suppressor whose mutations underlie a familial form of intestinal polyposis and colorectal cancers. In addition to its role in Wnt/β-catenin signaling, APC associates with microtubules and regulates cytoskeleton organization, cell polarity and migration in multiple cell types. Our laboratory showed that impairment of APC in T cells alters microtubule network and function of the transcription factor NFAT, leading to defective differentiation and cytokine production particularly in regulatory T lymphocytes (Tregs). The hypothesis of my PhD project is that APC-dependent alterations of cytoskeleton organization could impair anti-tumor immunity by affecting T cell ability to migrate into tumors, interact with cancer cells and kill them. To address these questions, I analysed chemokine- induced migration of T cell lines in transwell assays and observed that APC silencing impairs their specific migration. Real-time imaging of T cell motility highlighted that APC does not affect migration per se, but rather alters directional cell movement. Further analyses of cell polarization and 2D-3D morphology by imaging flow cytometry and confocal microscopy indicate that APC controls T cell 3D conformation and it is involved in actin-rich blebs formation and cortical rigidity, possibly helping in converting environmental cues into proper mechanical forces to insure directional cell locomotion. Preliminary observations also suggest the involvement of APC in T cell adhesion. Therefore, kinetics and strength of cell adhesion in living conditions are currently under measurement. Similar differences in migration and polarization, although to a lower extent, have been observed when comparing CD8 + T cells from control and APC-mutant mice. These studies will be soon extended to T cells from familial polyposis patients. Together, these results suggest that APC, by regulating both actin and microtubule cytoskeleton, is involved in both T cell motility and chemokine-induced polarity, which are crucial for productive anti-tumor immune responses. 2 Sorbonne Université, Collège Doctoral, Paris, France 3 Institut Pasteur, Cell Biology and Infection, Paris, France 4 Institut Cochin, Paris, France

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