Loss of DLG5 promotes breast cancer malignancy by inhibiting the Hippo signaling pathway
Menée in vitro et in vivo sur des modèles de cancer du sein, cette étude met en évidence des mécanismes par lesquels, en inhibant la voie de signalisation Hippo et en augmentant le niveau de la protéine YAP dans le noyau cellulaire, la perte d'expression du gène DLG5 favorise la progression d'une tumeur
Discs Large Homolog 5 (DLG5) plays an important role in the maintenance of epithelial cell polarity. Recent research showed that DLG5 is decreased in Yes-associated protein (YAP)-overexpressing cells. However, the exact relationship between DLG5 and YAP is not clear. In this study, we showed that loss of DLG5 promoted breast cancer cell proliferation by inhibiting the Hippo signaling pathway and increasing nuclear YAP expression. Furthermore, depletion of DLG5 induced epithelial-mesenchymal transition (EMT) and disrupted epithelial cell polarity, which was associated with altered expression of Scribble, ZO1, E-cadherin and N-cadherin and their mislocalization. Interestingly, we first reported that loss of DLG5 inhibited the interaction of Mst1 and Lats1 with Scribble, which was crucial for YAP activation and the transcription of TEA domain (TEAD) family members. In summary, loss of DLG5 expression promoted breast cancer malignancy by inactivating the Hippo signaling pathway and increasing nuclear YAP.