Oral communication, CS20 / C93

Official XXIst International Pigment Cell Conference website - 21-24 Sept 2011, Bordeaux - France | updated: September 04 2011

Differential LEF1 and TCF4 expression is involved in melanoma cell phenotype switching

The phenotype switching model for melanoma progression holds that melanoma cells, in response to microenvironmentally-regulated changes in signalling, switch back-and-forth between states of proliferation and invasion to drive metastatic spread. Proliferative phenotype melanoma cells show up-regulation of melanocytic marker genes, while the invasive phenotype cells show up-regulation of factors involved in modifying the extracellular environment. Furthermore, proliferative and invasive expression signatures correlate with specific characteristics of in vitro behaviour. Since canonical Wnt signaling has been shown to be important for melanocytic gene expression, survival and proliferation, phenotype switching has been linked to changes in Wnt signalling. Therefore we looked for cell phenotype-specific differences in the expression levels and activity of beta-catenin and its LEF/TCF co-factors. This showed that beta-catenin nuclear distribution and activity is not phenotype-specific. Conversely, we found the expression of LEF1 and TCF4 to be both phenotype-specific and anti-correlated. LEF1 is preferentially expressed by proliferative phenotype cells and TCF4 by invasive phenotype cells. Knock-down experiments confirmed that these co-factors are important for the phenotype-specific expression and behaviour, and that LEF1 suppresses TCF4 expression independently of beta-catenin. Our data shows that melanoma cell phenotype switching behaviour is regulated by differential LEF1/TCF4 activity.

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