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Loss of tumorigenic potential upon transdifferentiation from keratinocytic into melanocytic lineage

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. H...

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Autores principales: Fehrenbach, Sabrina, Novak, Daniel, Bernhardt, Mathias, Larribere, Lionel, Boukamp, Petra, Umansky, Viktor, Utikal, Jochen
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4937495/
https://www.ncbi.nlm.nih.gov/pubmed/27387763
http://dx.doi.org/10.1038/srep28891
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author Fehrenbach, Sabrina
Novak, Daniel
Bernhardt, Mathias
Larribere, Lionel
Boukamp, Petra
Umansky, Viktor
Utikal, Jochen
author_facet Fehrenbach, Sabrina
Novak, Daniel
Bernhardt, Mathias
Larribere, Lionel
Boukamp, Petra
Umansky, Viktor
Utikal, Jochen
author_sort Fehrenbach, Sabrina
collection PubMed
description 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.
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spelling pubmed-49374952016-07-18 Loss of tumorigenic potential upon transdifferentiation from keratinocytic into melanocytic lineage Fehrenbach, Sabrina Novak, Daniel Bernhardt, Mathias Larribere, Lionel Boukamp, Petra Umansky, Viktor Utikal, Jochen Sci Rep Article 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. Nature Publishing Group 2016-07-08 /pmc/articles/PMC4937495/ /pubmed/27387763 http://dx.doi.org/10.1038/srep28891 Text en Copyright © 2016, Macmillan Publishers Limited http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
spellingShingle Article
Fehrenbach, Sabrina
Novak, Daniel
Bernhardt, Mathias
Larribere, Lionel
Boukamp, Petra
Umansky, Viktor
Utikal, Jochen
Loss of tumorigenic potential upon transdifferentiation from keratinocytic into melanocytic lineage
title Loss of tumorigenic potential upon transdifferentiation from keratinocytic into melanocytic lineage
title_full Loss of tumorigenic potential upon transdifferentiation from keratinocytic into melanocytic lineage
title_fullStr Loss of tumorigenic potential upon transdifferentiation from keratinocytic into melanocytic lineage
title_full_unstemmed Loss of tumorigenic potential upon transdifferentiation from keratinocytic into melanocytic lineage
title_short Loss of tumorigenic potential upon transdifferentiation from keratinocytic into melanocytic lineage
title_sort loss of tumorigenic potential upon transdifferentiation from keratinocytic into melanocytic lineage
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4937495/
https://www.ncbi.nlm.nih.gov/pubmed/27387763
http://dx.doi.org/10.1038/srep28891
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