Yin Yang 1 orchestrates a metabolic program required for bothneural crest development and melanoma formation
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Date
2019-04-04Type
- Journal Article
Citations
Cited 26 times in
Web of Science
Cited 29 times in
Scopus
ETH Bibliography
yes
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Abstract
Increasing evidence suggests that cancer cells highjack
developmental programs for disease initiation and progression.
Melanoma arises from melanocytes that originate during
development from neural crest stem cells (NCSCs). Here, we
identified the transcription factor Yin Yang 1 (Yy1) as an NCSCs
regulator. Conditional deletion of Yy1 in NCSCs resulted in
stage-dependent hypoplasia of all major neural crest derivatives
due to decreased proliferation and increased cell death.
Moreover, conditional ablation of one Yy1 allele in a melanoma
mouse model prevented tumorigenesis, indicating a particular
susceptibility of melanoma cells to reduced Yy1 levels. Combined
RNA sequencing (RNA-seq), chromatin immunoprecipitation
(ChIP)-seq, and untargeted metabolomics demonstrated that YY1
governs multiple metabolic pathways and protein synthesis in
both NCSCs and melanoma. In addition to directly regulating a
metabolic gene set, YY1 can act upstream of MITF/c-MYC as part
of a gene regulatory network controlling metabolism. Thus, both
NCSC development and melanoma formation depend on an intricate
YY1-controlled metabolic program. Show more
Publication status
publishedExternal links
Journal / series
Cell Stem CellVolume
Pages / Article No.
Publisher
Cell PressSubject
YY1; development; melanoma; metabolism; neural crest; protein synthesis; tumor initiationOrganisational unit
08839 - Zamboni, Nicola (Tit.-Prof.)
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Show all metadata
Citations
Cited 26 times in
Web of Science
Cited 29 times in
Scopus
ETH Bibliography
yes
Altmetrics