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

被引：289

作者：

Damsky, William E. ^{[1
,3
]}

Curley, David P. ^{[3
,4
]}

Santhanakrishnan, Manjula ^{[1
]}

Rosenbaum, Lara E. ^{[1
]}

Platt, James T. ^{[1
]}

Rothberg, Bonnie E. Gould ^{[2
]}

Taketo, Makoto M. ^{[5
]}

Dankort, David ^{[6
]}

Rimm, David L. ^{[2
]}

McMahon, Martin ^{[7
,8
,9
]}

Bosenberg, Marcus ^{[1
,2
]}

机构：

[1] Yale Univ, Sch Med, Dept Dermatol, New Haven, CT 06510 USA

[2] Yale Univ, Sch Med, Dept Pathol, New Haven, CT 06510 USA

[3] Univ Vermont, Coll Med, Dept Pathol, Burlington, VT 05405 USA

[4] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA

[5] Kyoto Univ, Grad Sch Med, Dept Pharmacol, Kyoto 6068501, Japan

[6] McGill Univ, Dept Biol, Montreal, PQ H3G 0B1, Canada

[7] Univ Calif San Francisco, Canc Res Inst, San Francisco, CA 94143 USA

[8] Univ Calif San Francisco, Dept Cell & Mol Pharmacol, San Francisco, CA 94143 USA

[9] Univ Calif San Francisco, Helen Diller Family Comprehens Canc Ctr, San Francisco, CA 94143 USA

来源：

CANCER CELL | 2011年 / 20卷 / 06期

关键词：

CUTANEOUS MALIGNANT-MELANOMA; TRANSCRIPTION FACTOR; TISSUE MICROARRAY; TUMOR PROGRESSION; EXON-3; MUTATIONS; E-CADHERIN; EXPRESSION; SURVIVAL; GENE; DIFFERENTIATION;

D O I：

10.1016/j.ccr.2011.10.030

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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 Braf(V600E) 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.

引用

页码：741 / 754

页数：14

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