NFE2L3 Controls Colon Cancer Cell Growth through Regulation of DUX4, a CDK1 Inhibitor.
Adenocarcinoma
/ genetics
Animals
Basic-Leucine Zipper Transcription Factors
/ genetics
CDC2 Protein Kinase
/ antagonists & inhibitors
Cell Cycle Checkpoints
/ genetics
Cell Line, Tumor
Cell Proliferation
/ genetics
Chromatin Immunoprecipitation Sequencing
Colonic Neoplasms
/ genetics
Gene Expression Regulation, Neoplastic
/ genetics
Gene Knockdown Techniques
Gene Silencing
Homeodomain Proteins
/ genetics
Humans
Mass Spectrometry
Mice
Mice, Nude
NF-kappa B
/ metabolism
RNA, Small Interfering
Signal Transduction
/ genetics
Transcription Factor RelA
/ genetics
Transplantation, Heterologous
CDK inhibitor
CDK1
DUX4
NF-κB
NFE2L3
cell cycle
colorectal cancer
Journal
Cell reports
ISSN: 2211-1247
Titre abrégé: Cell Rep
Pays: United States
ID NLM: 101573691
Informations de publication
Date de publication:
05 11 2019
05 11 2019
Historique:
received:
12
07
2018
revised:
26
06
2019
accepted:
27
09
2019
entrez:
7
11
2019
pubmed:
7
11
2019
medline:
25
9
2020
Statut:
ppublish
Résumé
Constitutive nuclear factor κB (NF-κB) activation is a hallmark of colon tumor growth. Cyclin-dependent kinases (CDKs) are critical cell-cycle regulators, and inhibition of CDK activity has been used successfully as anticancer therapy. Here, we show that the NFE2L3 transcription factor functions as a key regulator in a pathway that links NF-κB signaling to the control of CDK1 activity, thereby driving colon cancer cell proliferation. We found that NFE2L3 expression is regulated by the RELA subunit of NF-κB and that NFE2L3 levels are elevated in patients with colon adenocarcinoma when compared with normal adjacent tissue. Silencing of NFE2L3 significantly decreases colon cancer cell proliferation in vitro and tumor growth in vivo. NFE2L3 knockdown results in increased levels of double homeobox factor 4 (DUX4), which functions as a direct inhibitor of CDK1. The discovered oncogenic pathway governing cell-cycle progression may open up unique avenues for precision cancer therapy.
Identifiants
pubmed: 31693889
pii: S2211-1247(19)31291-4
doi: 10.1016/j.celrep.2019.09.087
pii:
doi:
Substances chimiques
Basic-Leucine Zipper Transcription Factors
0
DUX4L1 protein, human
0
Homeodomain Proteins
0
NF-kappa B
0
NFE2L3 protein, human
0
RELA protein, human
0
RNA, Small Interfering
0
Transcription Factor RelA
0
CDC2 Protein Kinase
EC 2.7.11.22
CDK1 protein, human
EC 2.7.11.22
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1469-1481.e9Subventions
Organisme : CIHR
Pays : Canada
Informations de copyright
Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.