MSX1-Induced Neural Crest-Like Reprogramming Promotes Melanoma Progression

Markus V. Heppt, Joshua X. Wang, Denitsa M. Hristova, Zhi Wei, Ling Li, Brianna Evans, Marilda Beqiri, Samir Zaman, Jie Zhang, Martin Irmler, Carola Berking, Robert Besch, Johannes Beckers, Frank J. Rauscher, Rick A. Sturm, David E. Fisher, Meenhard Herlyn, Mizuho Fukunaga-Kalabis

Research output: Contribution to journalArticlepeer-review

15 Scopus citations

Abstract

Melanoma cells share many biological properties with neural crest stem cells. Here we show that the homeodomain transcription factor MSX1, which is significantly correlated with melanoma disease progression, reprograms melanocytes and melanoma cells toward a neural crest precursor-like state. MSX1-reprogrammed normal human melanocytes express the neural crest marker p75 and become multipotent. MSX1 induces a phenotypic switch in melanoma, which is characterized by an oncogenic transition from an E-cadherin–high nonmigratory state toward a ZEB1-high invasive state. ZEB1 up-regulation is responsible for the MSX1-induced migratory phenotype in melanoma cells. Depletion of MSX1 significantly inhibits melanoma metastasis in vivo. These results show that neural crest-like reprogramming achieved by a single factor is a critical process for melanoma progression.

Original languageEnglish (US)
Pages (from-to)141-149
Number of pages9
JournalJournal of Investigative Dermatology
Volume138
Issue number1
DOIs
StatePublished - Jan 2018

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Dermatology
  • Cell Biology

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