HSP90 facilitates oncogenic alterations of metabolism in B-cell lymphomas
Calvo-Vidal, M. N.; Zamponi, N.; Krumsiek, J.; Stockslager, M. A.; Revuelta, M. V.; Phillip, J. M.; Marullo, R.; Kotlov, N.; Patel, J.; Yang, S. N.; Yang, L.; Taldone, T.; Thieblemont, C.; Leonard, J. P.; Martin, P.; Inghirami, G.; Chiosis, G.; Manalis, S. R.; Cerchietti, L.
Show abstract
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 a novel role of HSP90 in the cytosolic compartmentalization of metabolic pathways in proliferating cancer cells. We found that HSP90 assists in the organization of metabolic enzymes into non-membrane-bound functional compartments termed metabosomes. Under experimental conditions that conserved the cellular proteostasis, we demonstrated that the compartmentalizing activity of HSP90 is critical to sustain the coordinated synthesis of multiple metabolites required for energy production, maintenance of the cellular biomass and secretion of immunometabolites. Conversely, inhibition of the nucleating capacity of HSP90 modified the topology of cytosolic metabosomes before protein degradation was apparent decreasing the efficiency of MYC-driven metabolic pathways. Inhibition of HSP90 decreases cancer metabolism in B-cell lymphoma cells and patients providing a novel mechanism of activity for this class of drugs.
Matching journals
The top 11 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- Targeting the MYC interaction network in B-cell lymphoma via histone deacetylase 6 inhibition 95%
- Methylmalonic acid induces metabolic abnormalities and exhaustion in CD8+ T cells to suppress anti-tumor immunity 94%
- Loss of EIF4G2 Mediates Aggressiveness in Distinct Human Endometrial Cancer Subpopulations with Poorer Survival Outcome in Patients 93%
Similar papers in this journal
- Targeting mitochondrial respiration and the BCL2 family in MYC-associated B-cell lymphoma 94%
- Cysteine is a limiting factor for glioma proliferation and survival 94%
- Inhibition of Acyl-CoA Synthetase Long Chain Isozymes Decreases Multiple Myeloma Cell Proliferation and Causes Mitochondrial Dysfunction 94%
Similar papers in this journal
- WNT4 regulates cellular metabolism via intracellular activity at the mitochondria in breast and gynecologic cancers 95%
- Novel spirocyclic dimer, SpiD3, targets chronic lymphocytic leukemia survival pathways with potent preclinical effects 94%
- Tumor suppressor PLK2 may serve as a biomarker in triple-negative breast cancer for improved response to PLK1 therapeutics 92%
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.