Cancer Cell
Volume 20, Issue 6, 13 December 2011, Pages 741-754
Journal home page for Cancer Cell

Article
β-Catenin Signaling Controls Metastasis in Braf-Activated Pten-Deficient Melanomas

https://doi.org/10.1016/j.ccr.2011.10.030Get rights and content
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Summary

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 β-catenin levels in a mouse model of melanoma that is based on melanocyte-specific Pten loss and BrafV600E mutation, we demonstrate that β-catenin is a central mediator of melanoma metastasis to the lymph nodes and lungs. In addition to altering metastasis, β-catenin levels control tumor differentiation and regulate both MAPK/Erk and PI3K/Akt signaling. Highly metastatic tumors with β-catenin stabilization are very similar to a subset of human melanomas. Together these findings establish Wnt signaling as a metastasis regulator in melanoma.

Highlights

► β- catenin loss in Pten/Braf melanomas improves survival and inhibits metastasis ► β-catenin stabilization in Pten/Braf melanomas enhances metastasis ► Highly differentiated melanomas can be very metastatic in vivo ► β-catenin status in melanoma regulates PI3K/Akt and MAPK/Erk signaling

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