NELL2-cdc42 signaling regulates BAF complexes and Ewing sarcoma cell growth.
AC133 Antigen
/ metabolism
Actins
/ metabolism
Animals
Cell Line, Tumor
Cell Proliferation
Chromatin Assembly and Disassembly
Down-Regulation
Gene Expression Regulation, Neoplastic
Humans
Mice, SCID
Multiprotein Complexes
/ metabolism
Nerve Tissue Proteins
/ metabolism
Oncogene Proteins, Fusion
/ metabolism
Phenotype
Polymerization
Protein Subunits
/ metabolism
Proteomics
Proto-Oncogene Protein c-fli-1
/ metabolism
RNA-Binding Protein EWS
/ metabolism
Receptors, Cell Surface
/ metabolism
Sarcoma, Ewing
/ genetics
Signal Transduction
Up-Regulation
cdc42 GTP-Binding Protein
/ metabolism
BAF complex
CD133
Ewing sarcoma
NELL2
Robo3
cdc42
secretome proteomics
Journal
Cell reports
ISSN: 2211-1247
Titre abrégé: Cell Rep
Pays: United States
ID NLM: 101573691
Informations de publication
Date de publication:
06 07 2021
06 07 2021
Historique:
received:
28
01
2021
revised:
07
04
2021
accepted:
25
05
2021
entrez:
7
7
2021
pubmed:
8
7
2021
medline:
11
2
2022
Statut:
ppublish
Résumé
BAF chromatin remodeling complexes play important roles in chromatin regulation and cancer. Here, we report that Ewing sarcoma cells are dependent on the autocrine signaling mediated by NELL2, a secreted glycoprotein that has been characterized as an axon guidance molecule. NELL2 uses Robo3 as the receptor to transmit critical growth signaling. NELL2 signaling inhibits cdc42 and upregulates BAF complexes and EWS-FLI1 transcriptional output. We demonstrate that cdc42 is a negative regulator of BAF complexes, inducing actin polymerization and complex disassembly. Furthermore, we identify NELL2
Identifiants
pubmed: 34233189
pii: S2211-1247(21)00619-7
doi: 10.1016/j.celrep.2021.109254
pmc: PMC8312579
mid: NIHMS1722137
pii:
doi:
Substances chimiques
AC133 Antigen
0
Actins
0
EWS-FLI fusion protein
0
Multiprotein Complexes
0
NELL2 protein, human
0
Nerve Tissue Proteins
0
Oncogene Proteins, Fusion
0
Protein Subunits
0
Proto-Oncogene Protein c-fli-1
0
RNA-Binding Protein EWS
0
ROBO3 protein, human
0
Receptors, Cell Surface
0
cdc42 GTP-Binding Protein
EC 3.6.5.2
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
109254Subventions
Organisme : NCI NIH HHS
ID : P01 CA165995
Pays : United States
Organisme : NCRR NIH HHS
ID : S10 RR025111
Pays : United States
Organisme : NCI NIH HHS
ID : R21 CA202485
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA054174
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR001120
Pays : United States
Informations de copyright
Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of interests The authors declare no competing interests.
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