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HSP90 Molecular Chaperones, Metabolic Rewiring, and Epigenetics: Impact on Tumor Progression and Perspective for Anticancer Therapy

Laboratory of Pre-Clinical and Translational Research, IRCCS, Referral Cancer Center of Basilicata, 85028 Rionero in Vulture (PZ), Italy
Department of Molecular Medicine and Medical Biotechnology, University of Naples Federico II, 80131 Naples, Italy
Medical Oncology Unit, Department of Medical and Surgical Sciences, University of Foggia, 71100 Foggia, Italy
Authors to whom correspondence should be addressed.
These authors contributed equally to this work.
Cells 2019, 8(6), 532;
Received: 22 March 2019 / Revised: 30 May 2019 / Accepted: 31 May 2019 / Published: 3 June 2019
(This article belongs to the Special Issue Mitochondrial Metabolic Reprogramming and Nuclear Crosstalk in Cancer)
Heat shock protein 90 (HSP90) molecular chaperones are a family of ubiquitous proteins participating in several cellular functions through the regulation of folding and/or assembly of large multiprotein complexes and client proteins. Thus, HSP90s chaperones are, directly or indirectly, master regulators of a variety of cellular processes, such as adaptation to stress, cell proliferation, motility, angiogenesis, and signal transduction. In recent years, it has been proposed that HSP90s play a crucial role in carcinogenesis as regulators of genotype-to-phenotype interplay. Indeed, HSP90 chaperones control metabolic rewiring, a hallmark of cancer cells, and influence the transcription of several of the key-genes responsible for tumorigenesis and cancer progression, through either direct binding to chromatin or through the quality control of transcription factors and epigenetic effectors. In this review, we will revise evidence suggesting how this interplay between epigenetics and metabolism may affect oncogenesis. We will examine the effect of metabolic rewiring on the accumulation of specific metabolites, and the changes in the availability of epigenetic co-factors and how this process can be controlled by HSP90 molecular chaperones. Understanding deeply the relationship between epigenetic and metabolism could disclose novel therapeutic scenarios that may lead to improvements in cancer treatment. View Full-Text
Keywords: HSP90; molecular chaperone; metabolism; epigenetics HSP90; molecular chaperone; metabolism; epigenetics
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Condelli, V.; Crispo, F.; Pietrafesa, M.; Lettini, G.; Matassa, D.S.; Esposito, F.; Landriscina, M.; Maddalena, F. HSP90 Molecular Chaperones, Metabolic Rewiring, and Epigenetics: Impact on Tumor Progression and Perspective for Anticancer Therapy. Cells 2019, 8, 532.

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