NF-κB-p62-NRF2 survival signaling is associated with high ROR1 expression in chronic lymphocytic leukemia.
Antibodies, Monoclonal, Humanized
/ pharmacology
B-Cell Activating Factor
/ metabolism
Bridged Bicyclo Compounds, Heterocyclic
/ pharmacology
Cell Line, Tumor
Cell Survival
/ drug effects
Cytoprotection
/ drug effects
Gene Expression Regulation, Leukemic
Humans
Leukemia, Lymphocytic, Chronic, B-Cell
/ genetics
Mechanistic Target of Rapamycin Complex 1
/ metabolism
NF-E2-Related Factor 2
/ metabolism
NF-kappa B
/ metabolism
Neoplasm Proteins
/ genetics
Prodrugs
/ pharmacology
RNA, Messenger
/ genetics
Reactive Oxygen Species
/ metabolism
Receptor Tyrosine Kinase-like Orphan Receptors
/ metabolism
Sequestosome-1 Protein
/ metabolism
Signal Transduction
/ drug effects
Sulfonamides
/ pharmacology
Journal
Cell death and differentiation
ISSN: 1476-5403
Titre abrégé: Cell Death Differ
Pays: England
ID NLM: 9437445
Informations de publication
Date de publication:
07 2020
07 2020
Historique:
received:
18
07
2019
accepted:
10
01
2020
revised:
09
01
2020
pubmed:
30
1
2020
medline:
23
9
2021
entrez:
30
1
2020
Statut:
ppublish
Résumé
Progression of chronic lymphocytic leukemia (CLL) and resistance to therapy are affected by tumor microenvironmental factors. One such factor is B-cell activating factor (BAFF), a cytokine that is produced mainly by nurse-like cells (NLC) and enhances CLL cells survival and modulates response to therapy. In CLL cells, BAFF activates NF-κB signaling, but how NF-κB supports CLL survival is not entirely clear. In this study we show that BAFF induces accumulation of the signaling and autophagy adaptor p62/SQSTM1 in a manner dependent on NF-κB activation. p62 potentiates mTORC1 signaling and activates NRF2, the master regulator of the anti-oxidant response. We found that expression of NRF2 target genes, such as NAD(P)H quinone oxidoreductase 1 (NQO1), is particularly enriched in CLL cells with high ROR1 surface expression (ROR1
Identifiants
pubmed: 31992855
doi: 10.1038/s41418-020-0496-1
pii: 10.1038/s41418-020-0496-1
pmc: PMC7308363
doi:
Substances chimiques
Antibodies, Monoclonal, Humanized
0
B-Cell Activating Factor
0
Bridged Bicyclo Compounds, Heterocyclic
0
NF-E2-Related Factor 2
0
NF-kappa B
0
Neoplasm Proteins
0
Prodrugs
0
RNA, Messenger
0
Reactive Oxygen Species
0
SQSTM1 protein, human
0
Sequestosome-1 Protein
0
Sulfonamides
0
TNFSF13B protein, human
0
ROR1 protein, human
EC 2.7.10.1
Receptor Tyrosine Kinase-like Orphan Receptors
EC 2.7.10.1
Mechanistic Target of Rapamycin Complex 1
EC 2.7.11.1
cirmtuzumab
FEH7RQ7B3J
venetoclax
N54AIC43PW
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
2206-2216Subventions
Organisme : NIAID NIH HHS
ID : R37 AI043477
Pays : United States
Organisme : NIEHS NIH HHS
ID : P42 ES010337
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA236361
Pays : United States
Organisme : NCI NIH HHS
ID : R37 CA049870
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA023100
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI043477
Pays : United States
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