Oncogenic HSP90 facilitates metabolic alterations in aggressive B-cell lymphomas
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...
| Main Authors: | , , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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American Association for Cancer Research (AACR)
2021
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| Online Access: | https://hdl.handle.net/1721.1/132977 |
| _version_ | 1826209021940465664 |
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| author | 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 Yang, Shao Ning Yang, Lucy Taldone, Tony Thieblemont, Catherine Leonard, John P Martin, Peter Inghirami, Giorgio Chiosis, Gabriela Manalis, Scott R Cerchietti, Leandro |
| author2 | Massachusetts Institute of Technology. Department of Mechanical Engineering |
| author_facet | Massachusetts Institute of Technology. Department of Mechanical Engineering 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 Yang, Shao Ning Yang, Lucy Taldone, Tony Thieblemont, Catherine Leonard, John P Martin, Peter Inghirami, Giorgio Chiosis, Gabriela Manalis, Scott R Cerchietti, Leandro |
| author_sort | Calvo-Vidal, M Nieves |
| collection | MIT |
| description | 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. |
| first_indexed | 2024-09-23T14:16:07Z |
| format | Article |
| id | mit-1721.1/132977 |
| institution | Massachusetts Institute of Technology |
| language | English |
| last_indexed | 2024-09-23T14:16:07Z |
| publishDate | 2021 |
| publisher | American Association for Cancer Research (AACR) |
| record_format | dspace |
| spelling | mit-1721.1/1329772023-12-13T15:31:07Z Oncogenic HSP90 facilitates metabolic alterations in aggressive B-cell lymphomas 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 Yang, Shao Ning Yang, Lucy Taldone, Tony Thieblemont, Catherine Leonard, John P Martin, Peter Inghirami, Giorgio Chiosis, Gabriela Manalis, Scott R Cerchietti, Leandro Massachusetts Institute of Technology. Department of Mechanical Engineering Koch Institute for Integrative Cancer Research at MIT Massachusetts Institute of Technology. Department of Biological Engineering 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. 2021-10-15T13:56:42Z 2021-10-15T13:56:42Z 2021-09 2021-08 2021-10-15T13:14:50Z Article http://purl.org/eprint/type/JournalArticle 0008-5472 1538-7445 https://hdl.handle.net/1721.1/132977 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 en 10.1158/0008-5472.can-21-2734 Cancer Research Creative Commons Attribution-Noncommercial-Share Alike http://creativecommons.org/licenses/by-nc-sa/4.0/ application/pdf American Association for Cancer Research (AACR) Prof. Manolis |
| spellingShingle | 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 Yang, Shao Ning Yang, Lucy Taldone, Tony Thieblemont, Catherine Leonard, John P Martin, Peter Inghirami, Giorgio Chiosis, Gabriela Manalis, Scott R Cerchietti, Leandro Oncogenic HSP90 facilitates metabolic alterations in aggressive B-cell lymphomas |
| title | Oncogenic HSP90 facilitates metabolic alterations in aggressive B-cell lymphomas |
| title_full | Oncogenic HSP90 facilitates metabolic alterations in aggressive B-cell lymphomas |
| title_fullStr | Oncogenic HSP90 facilitates metabolic alterations in aggressive B-cell lymphomas |
| title_full_unstemmed | Oncogenic HSP90 facilitates metabolic alterations in aggressive B-cell lymphomas |
| title_short | Oncogenic HSP90 facilitates metabolic alterations in aggressive B-cell lymphomas |
| title_sort | oncogenic hsp90 facilitates metabolic alterations in aggressive b cell lymphomas |
| url | https://hdl.handle.net/1721.1/132977 |
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