Oncogenic HSP90 facilitates metabolic alterations in aggressive B-cell lymphomas

M. Nieves Calvo-Vidal, Nahuel Zamponi, Jan Krumsiek, Max A. Stockslager, Maria V. Revuelta, Jude M. Phillip, Rossella Marullo, Ekaterina Tikhonova, Nikita Kotlov, Jayeshkumar Patel, Shao Ning Yang, Lucy Yang, Tony Taldone, Catherine Thieblemont, John P. Leonard, Peter Martin, Giorgio Inghirami, Gabriela Chiosis, Scott R. Manalis, Leandro Cerchietti

Research output: Contribution to journalArticlepeer-review

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 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.

Original languageEnglish (US)
JournalCancer Research
Volume81
Issue number20
DOIs
StatePublished - Oct 15 2021
Externally publishedYes

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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