MSX1-induced neural crest-like reprogramming promotes melanoma progression

Autor: Johannes Beckers, Marilda Beqiri, Richard A. Sturm, Joshua X. Wang, Robert Besch, Carola Berking, Frank J. Rauscher, Samir Zaman, Meenhard Herlyn, Jie Zhang, Mizuho Fukunaga-Kalabis, Denitsa Hristova, Markus V. Heppt, Brianna Evans, Martin Irmler, David E. Fisher, Ling Li, Zhi Wei
Jazyk: angličtina
Rok vydání: 2018
Předmět:
0301 basic medicine
Skin Neoplasms
Cellular differentiation
Human Embryonic Stem Cells
Kaplan-Meier Estimate
Mice
SCID
Biochemistry
Metastasis
Mice
Cell Movement
Mice
Inbred NOD
RNA
Small Interfering
Melanoma
Liver Neoplasms
Neural crest
Cell Differentiation
Dermis
Cadherins
Cellular Reprogramming
Cell Transformation
Neoplastic
Neural Crest
Disease Progression
Melanocytes
RNA Interference
Stem cell
Reprogramming
Nerve Tissue Proteins
Dermatology
Receptors
Nerve Growth Factor
Biology
03 medical and health sciences
Antigens
CD
Cell Line
Tumor
medicine
Animals
Humans
Molecular Biology
neoplasms
MSX1 Transcription Factor
Cadherin
Zinc Finger E-box-Binding Homeobox 1
Cell Biology
medicine.disease
Embryonic stem cell
Xenograft Model Antitumor Assays
stomatognathic diseases
030104 developmental biology
HEK293 Cells
Immunology
Cancer research
Zdroj: J. Invest. Dermatol. 138, 141-149 (2018)
Popis: Melanoma cells share many biological properties with neural crest stem cells. Here we show that the homeodomain transcription factor Msh homeobox 1 (MSX1), which is significantly correlated with melanoma disease progression, reprograms melanocytes and melanoma cells towards 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 non-migratory state towards 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 demonstrate that neural crest-like reprogramming achieved by a single factor is a critical process for melanoma progression.
Databáze: OpenAIRE
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