β-catenin signaling controls metastasis in Braf-activated Pten-deficient melanomas.

Abstract:

: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 Braf(V600E) 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.

journal_name

Cancer Cell

journal_title

Cancer cell

authors

Damsky WE,Curley DP,Santhanakrishnan M,Rosenbaum LE,Platt JT,Gould Rothberg BE,Taketo MM,Dankort D,Rimm DL,McMahon M,Bosenberg M

doi

10.1016/j.ccr.2011.10.030

subject

Has Abstract

pub_date

2011-12-13 00:00:00

pages

741-54

issue

6

eissn

1535-6108

issn

1878-3686

pii

S1535-6108(11)00405-3

journal_volume

20

pub_type

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