title: Loss of tumorigenic potential upon transdifferentiation from keratinocytic into melanocytic lineage.
abstract: Lineage-specific transcription factors determine the cell fate during development. Direct conversion of several cell types into other lineages has been achieved by the overexpression of specific transcription factors. Even cancer cells have been demonstrated to be amenable to transdifferentiation. Here, we identified a distinct set of transcription factors, which are sufficient to transform cells of the keratinocytic lineage to melanocyte-like cells. Melanocyte marker expression was induced and melanosome formation was observed in non-tumorigenic keratinocytes (HaCaT) and tumorigenic squamous cell carcinoma (MET-4) cells. Moreover, reduced proliferation, cell metabolism, invasion and migration were measured in vitro in transdifferentiated MT-MET-4 cells. A loss of tumorigenic potential of squamous cell carcinoma cells could be due to the upregulation of the melanocyte differentiation associated gene IL-24. Our data show that cells from the keratinocytic lineage can be transdifferented into the melanocytic lineage and provide a proof of principle for a potential new therapeutic strategy.
authors.affiliation: Skin Cancer Unit, German Cancer Research Center (DKFZ), 69121 Heidelberg, Germany.|Department of Dermatology, Venereology and Allergology, University Medical Center Mannheim, Ruprecht-Karl University of Heidelberg, 68167 Mannheim, Germany.
authors.forename: Sabrina
authors.initials: S
authors.lastname: Fehrenbach
authors.affiliation: Skin Cancer Unit, German Cancer Research Center (DKFZ), 69121 Heidelberg, Germany.|Department of Dermatology, Venereology and Allergology, University Medical Center Mannheim, Ruprecht-Karl University of Heidelberg, 68167 Mannheim, Germany.
authors.forename: Daniel
authors.initials: D
authors.lastname: Novak
authors.affiliation: Skin Cancer Unit, German Cancer Research Center (DKFZ), 69121 Heidelberg, Germany.|Department of Dermatology, Venereology and Allergology, University Medical Center Mannheim, Ruprecht-Karl University of Heidelberg, 68167 Mannheim, Germany.
authors.forename: Mathias
authors.initials: M
authors.lastname: Bernhardt
authors.affiliation: Skin Cancer Unit, German Cancer Research Center (DKFZ), 69121 Heidelberg, Germany.|Department of Dermatology, Venereology and Allergology, University Medical Center Mannheim, Ruprecht-Karl University of Heidelberg, 68167 Mannheim, Germany.
authors.forename: Lionel
authors.initials: L
authors.lastname: Larribere
authors.affiliation: Genetics of Skin Carcinogenesis, German Cancer Research Center (DKFZ), 69121 Heidelberg, Germany.|IUF-Leibniz Research Institute for Environmental Medicine, 40021 Düsseldorf, Germany.
authors.forename: Petra
authors.initials: P
authors.lastname: Boukamp
authors.affiliation: Skin Cancer Unit, German Cancer Research Center (DKFZ), 69121 Heidelberg, Germany.|Department of Dermatology, Venereology and Allergology, University Medical Center Mannheim, Ruprecht-Karl University of Heidelberg, 68167 Mannheim, Germany.
authors.forename: Viktor
authors.initials: V
authors.lastname: Umansky
authors.affiliation: Skin Cancer Unit, German Cancer Research Center (DKFZ), 69121 Heidelberg, Germany.|Department of Dermatology, Venereology and Allergology, University Medical Center Mannheim, Ruprecht-Karl University of Heidelberg, 68167 Mannheim, Germany.
authors.forename: Jochen
authors.initials: J
authors.lastname: Utikal
mesh_terms: D000818:Animals; D063646:Carcinogenesis / Q000378:metabolism; D002294:Carcinoma, Squamous Cell / Q000378:metabolism*; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D019070:Cell Lineage; D002465:Cell Movement; D049109:Cell Proliferation; D054338:Cell Transdifferentiation; D002869:Chromosome Aberrations; D003001:Cloning, Molecular; D055028:Comparative Genomic Hybridization; D019175:DNA Methylation; D020869:Gene Expression Profiling; D006801:Humans; D007378:Interleukins / Q000378:metabolism; D015603:Keratinocytes / Q000166:cytology*; D008544:Melanocytes / Q000166:cytology*; D051379:Mice; D009361:Neoplasm Invasiveness; D009368:Neoplasm Transplantation; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D015398:Signal Transduction; D012878:Skin Neoplasms / Q000378:metabolism*; D000099180:Interleukin-24
chemical_list: D007378:Interleukins; D000099180:Interleukin-24