Oncogenic HSP90 facilitates metabolic alterations in aggressive B-cell lymphomas
Name
Oncogenic HSP90 AFM.pdf
Description
Accepted version
Size
2.78 MB
Format
Adobe PDF
Checksum (MD5)
247444ed6d94467881a9c36474319c06
Author(s)
Calvo-Vidal, M Nieves
Zamponi, Nahuel
Krumsiek, Jan
Stockslager, Max A
Revuelta, Maria V
Phillip, Jude M
Marullo, Rossella
Tikhonova, Ekaterina
Kotlov, Nikita
Patel, Jayeshkumar
Date Issued
September 2021
Journal
Cancer Research
Publisher
American Association for Cancer Research (AACR)
Citation
Calvo-Vidal, M. Nieves et al. Oncogenic HSP90 Facilitates Metabolic Alterations in Aggressive B-cell Lymphomas, Cancer Res October 15 2021 (81) (20) 5202-5216
Version
Author's final manuscript
Abstract
HSP90 is critical for the maintenance of 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 describe 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 the 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.
MIT Department
Massachusetts Institute of Technology. Department of Mechanical Engineering
Koch Institute for Integrative Cancer Research at MIT
Massachusetts Institute of Technology. Department of Biological Engineering
Terms of Use
Creative Commons Attribution-Noncommercial-Share Alike
Persistent DSpace Link
DOI of Published Version
https://doi.org/10.1158/0008-5472.can-21-2734
