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

doi:10.1016/j.jid.2017.05.038

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 journal › Article › peer-review

29 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 language	English (US)
Pages (from-to)	141-149
Number of pages	9
Journal	Journal of Investigative Dermatology
Volume	138
Issue number	1
DOIs	https://doi.org/10.1016/j.jid.2017.05.038
State	Published - Jan 2018
Externally published	Yes

All Science Journal Classification (ASJC) codes

Biochemistry
Molecular Biology
Dermatology
Cell Biology

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10.1016/j.jid.2017.05.038

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Heppt, M. V., Wang, J. X., Hristova, D. M., Wei, Z., Li, L., Evans, B., Beqiri, M., Zaman, S., Zhang, J., Irmler, M., Berking, C., Besch, R., Beckers, J., Rauscher, F. J., Sturm, R. A., Fisher, D. E., Herlyn, M., & Fukunaga-Kalabis, M. (2018). MSX1-Induced Neural Crest-Like Reprogramming Promotes Melanoma Progression. Journal of Investigative Dermatology, 138(1), 141-149. https://doi.org/10.1016/j.jid.2017.05.038

@article{f491046aebc04b99a82ff37936c58672,

title = "MSX1-Induced Neural Crest-Like Reprogramming Promotes Melanoma Progression",

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.",

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

note = "Publisher Copyright: {\textcopyright} 2017 The Authors",

year = "2018",

month = jan,

doi = "10.1016/j.jid.2017.05.038",

language = "English (US)",

volume = "138",

pages = "141--149",

journal = "Journal of Investigative Dermatology",

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Heppt, MV, Wang, JX, Hristova, DM, Wei, Z, Li, L, Evans, B, Beqiri, M, Zaman, S, Zhang, J, Irmler, M, Berking, C, Besch, R, Beckers, J, Rauscher, FJ, Sturm, RA, Fisher, DE, Herlyn, M & Fukunaga-Kalabis, M 2018, 'MSX1-Induced Neural Crest-Like Reprogramming Promotes Melanoma Progression', Journal of Investigative Dermatology, vol. 138, no. 1, pp. 141-149. https://doi.org/10.1016/j.jid.2017.05.038

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T1 - MSX1-Induced Neural Crest-Like Reprogramming Promotes Melanoma Progression

AU - Heppt, Markus V.

AU - Wang, Joshua X.

AU - Hristova, Denitsa M.

AU - Wei, Zhi

AU - Li, Ling

AU - Evans, Brianna

AU - Beqiri, Marilda

AU - Zaman, Samir

AU - Zhang, Jie

AU - Irmler, Martin

AU - Berking, Carola

AU - Besch, Robert

AU - Beckers, Johannes

AU - Rauscher, Frank J.

AU - Sturm, Rick A.

AU - Fisher, David E.

AU - Herlyn, Meenhard

AU - Fukunaga-Kalabis, Mizuho

PY - 2018/1

Y1 - 2018/1

N2 - 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.

AB - 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.

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MSX1-Induced Neural Crest-Like Reprogramming Promotes Melanoma Progression

Abstract

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