Beta-Catenin Signaling Controls Metastasis in Braf-Activated Pten-Deficient Melanomas
Menée à l'aide d'un modèle murin de mélanome présentant la mutation BrafV600E, cette étude met en évidence le rôle joué par la bêta-caténine dans le processus métastatique
Malignant melanoma is characterized by frequent metastasis, however, specific changes that regulate this process have not been clearly delineated. Although it is well known that Wnt signaling is frequently dysregulated in melanoma, the functional implications of this observation are unclear. By modulating beta-catenin levels in a mouse model of melanoma that is based on melanocyte-specific Pten loss and BrafV600E mutation, we demonstrate that beta-catenin is a central mediator of melanoma metastasis to the lymph nodes and lungs. In addition to altering metastasis, beta-catenin levels control tumor differentiation and regulate both MAPK/Erk and PI3K/Akt signaling. Highly metastatic tumors with beta-catenin stabilization are very similar to a subset of human melanomas. Together these findings establish Wnt signaling as a metastasis regulator in melanoma. ºbeta- catenin loss in Pten/Braf melanomas improves survival and inhibits metastasis ºbeta-catenin stabilization in Pten/Braf melanomas enhances metastasis º Highly differentiated melanomas can be very metastatic in vivo º beta-catenin status in melanoma regulates PI3K/Akt and MAPK/Erk signaling