Mechanisms that regulate epithelial to mesenchymal transition through the Met receptor
Zusammenfassung der Projektergebnisse
Signaling through the Met receptor is associated with tumorigenesis and leads to an EMT-like behaviour of cells in cell culture: Cells loose their cell-cell junctions and remodel their polarity, ultimately allowing them to migrate and invade into the surrounding matrix. The precise molecular mechanisms that link activation of Met and cellular polarity are however poorly understood. Here, we identify Scrib, a polarity protein, as a novel binding partner of the Met receptor. Scrib has been previously linked to tumorigenesis, making it an interesting candidate to perform functions downstream of Met signaling. We determine that Scrib binds Met constitutively and that Scrib PDZ domains 3 and 4 associate with Met. Both Met and Scrib co-localize at sites of cell-cell contact. We show that Scrib is required for efficient phosphorylation of Erk, the central kinase of the conserved MAP kinase pathway. This suggests that Scrib impinges on MAP kinase signaling, a pathway through which many of the downstream functions of Met receptor signaling are conveyed and a pathway that is affected in 30% of human cancers. In summary, we link oncogenic tyrosine kinase signaling physically and functionally to cell polarity. Our data may hence contribute to a better understanding of epithelial cancers.
Projektbezogene Publikationen (Auswahl)
- (2010) SpringerReference: Encyclopedia of Signaling Molecules: Gab1
Vaillancourt R, Spilker AC, Park M
