719A Poster - 11. Cell division and cell growth
Thursday April 07, 2:00 PM - 4:00 PM

Authors:
Marianne Montemurro; Bruno Monier; Magali Suzanne

Affiliation: Centre de Biologie Integrative CBI - Molecular, Cellular and Developmental Biology Unit - UMR 5077

Keywords:
r. tumor suppressors and oncogenes; h. other (Pro-tumoral role of cell death)

Cancer is a largely widespread pathology that corresponds to an overproliferation of cells that could finally invade others tissues. Tumors develop through three increasingly aggressive steps: (1) hyperplasia, which corresponds to cells overproliferation without any modification of epithelial properties; (2) neoplasia, during which cells can acquire a more mesenchymal phenotype, and finally (3) metastasis, when cells leave the primary tumor, migrate and form secondary tumors.
Tumor development can be influenced by mutations (or combination of mutations) but also by external factors, such as extracellular matrix rigidity. However, a comprehensive understanding of the factors driving tumor evolution is still lacking. My project aims to use Drosophila to identify unexpected factors that could influence tumor development, and more specifically the hyperplasia/neoplasia transition, a critical step in tumor aggressiveness. After an in-depth characterization of tumor progression at cellular level at successive timepoints, I selected two complementary genetic contexts for further analysis: a strictly hyperplasic tumor (“Yorkie overexpression” context) and an initially hyperplasic tumor that eventually evolves in neoplasia (“Avalanche loss-of-function” context).
Strikingly, I identified two new and unexpected factors involved in tumor progression and aggressiveness: apoptosis and tissue tension. Indeed, while tumor aggressiveness coincides with a high level of apoptotic cells, abolishing apoptosis in Avalanche tumors strongly decreases the hyperplasia/neoplasia shift, while introducing cell death in Yorkie tumors converts hyperplastic tissues into neoplastic ones. Hence, in those two different contexts, modulation of apoptosis surprisingly favors the hyperplasia/neoplasia transition. Moreover, I found that tumor aggressiveness is associated with high tissue tension and that increasing junctional tension (by modulating a Myosin II regulator) is sufficient to induce a hyperplasia/neoplasia transition in a tumor context normally strictly hyperplasic (Yorkie’s context). I am now characterizing whether cell death and tissue mechanics are linked or whether they act independently of one another to drive tumor progression.