Annuaire
Cyrille de Joussineau, Institut GReD : Génétique, Reproduction et Développement - Clermont Ferrand
| Quand ? |
Le 17/09/2025, de 14:00 à 15:00 |
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| S'adresser à | Salle des thèses, Equipe Mollereau |
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90% of all cancers are of epithelial origin. Technically, adenocarcinoma founding event occurs when a tumor cell leaves the epithelial compartment to invade neighboring tissues. This step, called epithelial basal extrusion, is mostly ignored due to its elusiveness. We have developed an in vivo model dedicated to its study in the drosophila equivalent of the prostate: the accessory gland. We have shown that tumor basal extrusion is molecularly controlled by PI3K/Akt and Ras/MAPK pathways via autocrine mechanisms, and relies also on cholesterol metabolism deregulation. Furthermore, our recent work indicates that this step could also be a major actor in resistance to treatment: by reproducing breast/prostate endocrine therapy, we show that repression of sex steroid signaling modifies basal extrusion, leading to the formation a new population of highly proliferative, resistant tumor cells. We are now searching for the molecular mechanisms that are mobilized to adapt a tumor cell to its treatment. Our current work indicates that the non-canonical Notch pathway controls the transdifferentiation of a tumor cell into a resistant tumor cell.
Thus, our work indicates that, in drosophila, basal extrusion is a highly controlled event leading to both tumor formation and tumor resistance. A better understanding of these mechanisms could open new fields of investigation to apprehend epithelial cancer progression.