Oncogenic HSP90 Facilitates Metabolic Alterations in Aggressive B-cell Lymphomas.
Journal
Cancer research
ISSN: 1538-7445
Titre abrégé: Cancer Res
Pays: United States
ID NLM: 2984705R
Informations de publication
Date de publication:
15 10 2021
15 10 2021
Historique:
received:
15
08
2021
revised:
30
08
2021
accepted:
01
09
2021
pubmed:
5
9
2021
medline:
7
1
2022
entrez:
4
9
2021
Statut:
ppublish
Résumé
HSP90 is critical for maintenance of the cellular proteostasis. In cancer cells, HSP90 also becomes a nucleating site for the stabilization of multiprotein complexes including signaling pathways and transcription complexes. Here we described the role of this HSP90 form, referred to as oncogenic HSP90, in the regulation of cytosolic metabolic pathways in proliferating B-cell lymphoma cells. Oncogenic HSP90 assisted in the organization of metabolic enzymes into non-membrane-bound functional compartments. Under experimental conditions that conserved cellular proteostasis, oncogenic HSP90 coordinated and sustained multiple metabolic pathways required for energy production and maintenance of cellular biomass as well as for secretion of extracellular metabolites. Conversely, inhibition of oncogenic HSP90, in absence of apparent client protein degradation, decreased the efficiency of MYC-driven metabolic reprogramming. This study reveals that oncogenic HSP90 supports metabolism in B-cell lymphoma cells and patients with diffuse large B-cell lymphoma, providing a novel mechanism of activity for HSP90 inhibitors. SIGNIFICANCE: The oncogenic form of HSP90 organizes and maintains functional multienzymatic metabolic hubs in cancer cells, suggesting the potential of repurposing oncogenic HSP90 selective inhibitors to disrupt metabolism in lymphoma cells.
Identifiants
pubmed: 34479963
pii: 0008-5472.CAN-21-2734
doi: 10.1158/0008-5472.CAN-21-2734
pmc: PMC8530929
mid: NIHMS1739552
doi:
Substances chimiques
HSP90 Heat-Shock Proteins
0
MYC protein, human
0
Proto-Oncogene Proteins c-myc
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
5202-5216Subventions
Organisme : NIA NIH HHS
ID : R01 AG067598
Pays : United States
Organisme : NCI NIH HHS
ID : P01 CA229100
Pays : United States
Organisme : NCI NIH HHS
ID : T32 CA203702
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA008748
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG074004
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA242069
Pays : United States
Organisme : NCI NIH HHS
ID : U54 CA217377
Pays : United States
Informations de copyright
©2021 The Authors; Published by the American Association for Cancer Research.
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