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

Ossia M. Eichhoff, Ashani Weeraratna, Marie C. Zipser, Laurence Denat, Daniel S. Widmer, Mai Xu, Lydia Kriegl, Thomas Kirchner, Lionel Larue, Reinhard Dummer, Keith S. Hoek

Research output: Contribution to journalArticlepeer-review

70 Scopus citations


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 β-catenin and its LEF/TCF co-factors. We found that while cytosolic β-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 β-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 β-catenin. Our data show that melanoma cell phenotype switching behaviour is regulated by differential LEF1/TCF4 activity.

Original languageEnglish (US)
Pages (from-to)631-642
Number of pages12
JournalPigment Cell and Melanoma Research
Issue number4
StatePublished - Aug 2011
Externally publishedYes


  • LEF1
  • MITF
  • Melanoma
  • TCF4
  • WNT5A

ASJC Scopus subject areas

  • Oncology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Dermatology


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