Line Chaar's PhD defense

During the neoplastic transformation, a solid-to-liquid transition can overcome the motility arrest of healthy, confluent epithelial cells, and promote tissue fluidization through large-scale collective cell migration. A balance between mechanical forces at cell–cell and cell–extracellular matrix is essential for tissue cohesiveness and for cooperative cell movement. However, integration of upstream morphogenic cues with downstream tissue mechanics remains understudied during collective cell migration. In the present work, we investigated whether and how BMP2, a TGFβ family member involved in breast cancer, may influence the coordination of cellular movement in breast epithelium. As contrary to TGFβ, BMP2 enhances cell coordination and sustains E-cadherin at cell-cell contact to support collective migration. This collective network migration and cell cluster migration in 2D induced by BMP2 is associated with a partial Epithelio-Mesenchymal Transition (EMT) of MCF10A cells. MCF10A cells adopt an elongated shape through junctional plasticity. BMP2-treated 3D breast acini undergo disorganisation of actin cytoskeleton and perturbation of the apico-basal polarity. The fluidization of MCF-10A monolayer required β1 integrin to control collective migration. Solid-liquid and acini-multi cellular aggregates transitions upon BMP2 stimulation are correlated with membrane deformations and a perturbed distribution of β1 integrin at cell-cell and cell-ECM contacts. Mechanistically, our results suggest that β1 integrin might contribute to epithelial tissue cohesion through the building of mechanosensitive structures to safeguard breast epithelium integrity.