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

• Published in: Cells (Basel, Switzerland) Vol. 8; no. 6; p. 532
• Main Authors: Condelli, Valentina, Crispo, Fabiana, Pietrafesa, Michele, Lettini, Giacomo, Matassa, Danilo Swann, Esposito, Franca, Landriscina, Matteo, Maddalena, Francesca
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 03.06.2019; MDPI
• Subjects: Adaptation; Adenosine triphosphate; Angiogenesis; Animals; Antineoplastic Agents - pharmacology; Antineoplastic Agents - therapeutic use; Cancer; Cancer therapies; Carcinogenesis; Cell growth; Cell proliferation; Chaperones; Chromatin; Deoxyribonucleic acid; Disease Progression; DNA; DNA methylation; Epigenesis, Genetic - drug effects; Epigenetics; Gene expression; Genotypes; Heat shock proteins; Homeostasis; HSP90; HSP90 Heat-Shock Proteins - metabolism; Hsp90 protein; Humans; Medical prognosis; Metabolism; Metabolites; molecular chaperone; Neoplasms - drug therapy; Neoplasms - genetics; Pancreatic cancer; Phenotype; Phenotypes; Phosphorylation; Quality control; Review; Signal transduction; Transcription factors; Transduction; Tumorigenesis; Italy; HSP90; molecular chaperone; metabolism; epigenetics
• ISSN: 2073-4409; 2073-4409
• DOI: 10.3390/cells8060532

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.