β-Catenin Signaling Increases during Melanoma Progression and Promotes Tumor Cell Survival and Chemoresistance
Open Access
- 17 August 2011
- journal article
- research article
- Published by Public Library of Science (PLoS) in PLOS ONE
- Vol. 6 (8), e23429
- https://doi.org/10.1371/journal.pone.0023429
Abstract
Beta-catenin plays an important role in embryogenesis and carcinogenesis by controlling either cadherin-mediated cell adhesion or transcriptional activation of target gene expression. In many types of cancers nuclear translocation of beta-catenin has been observed. Our data indicate that during melanoma progression an increased dependency on the transcriptional function of beta-catenin takes place. Blockade of beta-catenin in metastatic melanoma cell lines efficiently induces apoptosis, inhibits proliferation, migration and invasion in monolayer and 3-dimensional skin reconstructs and decreases chemoresistance. In addition, subcutaneous melanoma growth in SCID mice was almost completely inhibited by an inducible beta-catenin knockdown. In contrast, the survival of benign melanocytes and primary melanoma cell lines was less affected by beta-catenin depletion. However, enhanced expression of beta-catenin in primary melanoma cell lines increased invasive capacity in vitro and tumor growth in the SCID mouse model. These data suggest that beta-catenin is an essential survival factor for metastatic melanoma cells, whereas it is dispensable for the survival of benign melanocytes and primary, non-invasive melanoma cells. Furthermore, beta-catenin increases tumorigenicity of primary melanoma cell lines. The differential requirements for beta-catenin signaling in aggressive melanoma versus benign melanocytic cells make beta-catenin a possible new target in melanoma therapy.This publication has 57 references indexed in Scilit:
- A Re-evaluation of the “Oncogenic” Nature of Wnt/β-catenin Signaling in Melanoma and Other CancersCurrent Oncology Reports, 2010
- NF2-deficient cells depend on the Rac1-canonical Wnt signaling pathway to promote the loss of contact inhibition of proliferationOncogene, 2010
- Hear the Wnt Ror: how melanoma cells adjust to changes in WntPigment Cell & Melanoma Research, 2009
- Wnt-5a-CKIα Signaling Promotes β-Catenin/E-Cadherin Complex Formation and Intercellular Adhesion in Human Breast Epithelial CellsOnline Journal of Public Health Informatics, 2009
- Activated Wnt/ß-catenin signaling in melanoma is associated with decreased proliferation in patient tumors and a murine melanoma modelProceedings of the National Academy of Sciences of the United States of America, 2009
- β-Catenin is a Nek2 substrate involved in centrosome separationGenes & Development, 2007
- β-Catenin induces immortalization of melanocytes by suppressing p16INK4a expression and cooperates with N-Ras in melanoma developmentGenes & Development, 2007
- Targeting the β-catenin/TCF transcriptional complex in the treatment of multiple myelomaProceedings of the National Academy of Sciences of the United States of America, 2007
- Pax3 functions at a nodal point in melanocyte stem cell differentiationNature, 2005
- WNT and β-catenin signalling: diseases and therapiesNature Reviews Genetics, 2004