Seminar by Clementine Villeneuve
Date and time: Wednesday 28th August at 12:00 pm in the Turku Bioscience 7th floor big seminar room (A-side).
Speaker: Clémentine Villeneuve from Philip Chavrier’s group (Institut Curie Research Centre, France)
Tentative title: aPKCi triggers basal extrusion and early cell dissemination by modulating vinculin localisation and contractility at cell-cell junction.
Metastasis is the main cause of cancer-related deaths. Recent data suggest that metastatic dissemination often occurs at an early stage during tumour formation. Tumorigenesis is a multi-step process that is initiated from oncogenic single cells within a normal tissue. How these cancer cell alterations evolve within a tightly regulated normal tissue environment remains unknown. Cell extrusion is a potential mechanism that allows for mutant cells to escape from untransformed epithelia, and the cues promoting tumor cell extrusion need to be identified. Polarity proteins may play essential roles in triggering cell extrusion and early tumor cell dissemination as loss of epithelial cell polarity is a hallmark of cancer cells that is correlated with tumor aggressiveness. The polarity protein kinase aPKCi (atypical Protein Kinase C iota) is an oncogene and its overexpression (aPKCi+) is linked to poor prognosis. Here, we identify aPKCi+ oncogenic basal extrusion from the normal mammary epithelium as a mechanism for early breast tumor cell dissemination in vivo. By combining in vitro biophysical approaches, we show an increase in cell tension at the interface between aPKCi+ and WT cells. This increase in cell tension depends on myosin II activity and is associated with the relocation of vinculin from cell-cell junctions to focal adhesions in aPKCi+ cells. The shift in vinculin localization affects aPKCi+/WT cell junction stability, leading to the acquisition of pro-migratory features in aPKCi+ cells. We propose that a balance between cell contractility and cell-cell adhesion at the interface of normal and oncogenic aPKCi+ cells is crucial for promoting basal cell extrusion. We anticipate that this mechanism may be conserved in other carcinomas, promoting early cancer cell dissemination.