Nuclear Dishevelled targets gene regulatory regions and promotes tumor growth.
ChIP-seq
DVL
Wnt
breast cancer
epigenetics
Journal
EMBO reports
ISSN: 1469-3178
Titre abrégé: EMBO Rep
Pays: England
ID NLM: 100963049
Informations de publication
Date de publication:
04 06 2021
04 06 2021
Historique:
revised:
03
03
2021
received:
07
04
2020
accepted:
11
03
2021
pubmed:
17
4
2021
medline:
29
6
2021
entrez:
16
4
2021
Statut:
ppublish
Résumé
Dishevelled (DVL) critically regulates Wnt signaling and contributes to a wide spectrum of diseases and is important in normal and pathophysiological settings. However, how it mediates diverse cellular functions remains poorly understood. Recent discoveries have revealed that constitutive Wnt pathway activation contributes to breast cancer malignancy, but the mechanisms by which this occurs are unknown and very few studies have examined the nuclear role of DVL. Here, we have performed DVL3 ChIP-seq analyses and identify novel target genes bound by DVL3. We show that DVL3 depletion alters KMT2D binding to novel targets and changes their epigenetic marks and mRNA levels. We further demonstrate that DVL3 inhibition leads to decreased tumor growth in two different breast cancer models in vivo. Our data uncover new DVL3 functions through its regulation of multiple genes involved in developmental biology, antigen presentation, metabolism, chromatin remodeling, and tumorigenesis. Overall, our study provides unique insight into the function of nuclear DVL, which helps to define its role in mediating aberrant Wnt signaling.
Identifiants
pubmed: 33860601
doi: 10.15252/embr.202050600
pmc: PMC8183407
doi:
Substances chimiques
Dishevelled Proteins
0
Phosphoproteins
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e50600Subventions
Organisme : NIH HHS
ID : S10 OD025115
Pays : United States
Organisme : NIDA NIH HHS
ID : R01 DA044999
Pays : United States
Organisme : Cancer Prevention and Research Institute of Texas (CPRIT)
ID : RR140008
Organisme : NCI NIH HHS
ID : R01 CA155223
Pays : United States
Organisme : HHS | NIH | National Institute on Drug Abuse (NIDA)
ID : DA 044999-01A1
Informations de copyright
© 2021 The Authors.
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