Journal
PIGMENT CELL & MELANOMA RESEARCH
Volume 24, Issue 4, Pages 631-642Publisher
WILEY
DOI: 10.1111/j.1755-148X.2011.00871.x
Keywords
melanoma; LEF1; TCF4; MITF; WNT5A
Categories
Funding
- Swiss National Science Foundation [320030-119989]
- Julia Bangerter Rhyner Stiftung
- National Institute on Aging
- Swiss National Science Foundation (SNF) [320030-119989] Funding Source: Swiss National Science Foundation (SNF)
Ask authors/readers for more resources
Recent observations suggest that melanoma cells drive disease progression by switching back and forth between phenotypic states of proliferation and invasion. Phenotype switching has been linked to changes in Wnt signalling, and we therefore looked for cell phenotype-specific differences in the levels and activity of beta-catenin and its LEF/TCF co-factors. We found that while cytosolic beta-catenin distribution is phenotype-specific (membrane-associated in proliferative cells and cytosolic in invasive cells), its nuclear distribution and activity is not. Instead, the expression patterns of two beta-catenin co-factors, LEF1 and TCF4, are both phenotype-specific and inversely correlated. LEF1 is preferentially expressed by differentiated/proliferative phenotype cells and TCF4 by dedifferentiated/invasive phenotype cells. Knock-down experiments confirmed that these co-factors are important for the phenotype-specific expression of M-MITF, WNT5A and other genes and that LEF1 suppresses TCF4 expression independently of beta-catenin. Our data show that melanoma cell phenotype switching behaviour is regulated by differential LEF1/TCF4 activity.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available