Circulating Tumor Cell Clustering Shapes DNA Methylation to Enable Metastasis Seeding.
Animals
Breast Neoplasms
/ genetics
Cell Differentiation
Cell Line, Tumor
Cell Proliferation
DNA Methylation
/ physiology
Disease Models, Animal
Female
Humans
Mice
Mice, Inbred NOD
Nanog Homeobox Protein
/ metabolism
Neoplasm Metastasis
/ genetics
Neoplastic Cells, Circulating
/ metabolism
Octamer Transcription Factor-3
/ metabolism
Repressor Proteins
/ metabolism
SOXB1 Transcription Factors
/ metabolism
Sin3 Histone Deacetylase and Corepressor Complex
RNA sequencing
bisulfite sequencing
circulating tumor cell clusters
circulating tumor cells
drug screen
proliferation-associated transcription factors
single cell sequencing
stemness-associated transcription factors
Journal
Cell
ISSN: 1097-4172
Titre abrégé: Cell
Pays: United States
ID NLM: 0413066
Informations de publication
Date de publication:
10 01 2019
10 01 2019
Historique:
received:
14
06
2018
revised:
31
08
2018
accepted:
28
11
2018
entrez:
12
1
2019
pubmed:
12
1
2019
medline:
14
11
2019
Statut:
ppublish
Résumé
The ability of circulating tumor cells (CTCs) to form clusters has been linked to increased metastatic potential. Yet biological features and vulnerabilities of CTC clusters remain largely unknown. Here, we profile the DNA methylation landscape of single CTCs and CTC clusters from breast cancer patients and mouse models on a genome-wide scale. We find that binding sites for stemness- and proliferation-associated transcription factors are specifically hypomethylated in CTC clusters, including binding sites for OCT4, NANOG, SOX2, and SIN3A, paralleling embryonic stem cell biology. Among 2,486 FDA-approved compounds, we identify Na
Identifiants
pubmed: 30633912
pii: S0092-8674(18)31571-X
doi: 10.1016/j.cell.2018.11.046
pmc: PMC6363966
pii:
doi:
Substances chimiques
NANOG protein, human
0
Nanog Homeobox Protein
0
Octamer Transcription Factor-3
0
POU5F1 protein, human
0
Repressor Proteins
0
SIN3A transcription factor
0
SOX2 protein, human
0
SOXB1 Transcription Factors
0
Sin3 Histone Deacetylase and Corepressor Complex
EC 3.5.1.98
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
98-112.e14Subventions
Organisme : European Research Council
ID : 678834
Pays : International
Informations de copyright
Copyright © 2018 Elsevier Inc. All rights reserved.
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