Histone deacetylase 10 promotes autophagy-mediated cell survival

• Verfasst von: Oehme, Ina [VerfasserIn]
• Verfasst von: Linke, Jan-Peter [VerfasserIn]
• Verfasst von: Böck, Barbara [VerfasserIn]
• Verfasst von: Milde, Till [VerfasserIn]
• Verfasst von: Lodrini, Marco [VerfasserIn]
• Verfasst von: Hartenstein, Bettina [VerfasserIn]
• Verfasst von: Rettig, Inga Edeltraud [VerfasserIn]
• Verfasst von: Eckert, Christian [VerfasserIn]
• Verfasst von: Roth, Wilfried [VerfasserIn]
• Verfasst von: Kool, Marcel [VerfasserIn]
• Verfasst von: Kaden, Sylvia [VerfasserIn]
• Verfasst von: Gröne, Hermann-Josef [VerfasserIn]
• Verfasst von: Schulte, Johannes Hubertus [VerfasserIn]
• Verfasst von: Lindner, Sven [VerfasserIn]
• Verfasst von: Hamacher-Brady, Anne [VerfasserIn]
• Verfasst von: Brady, Nathan [VerfasserIn]
• Verfasst von: Deubzer, Hedwig [VerfasserIn]
• Verfasst von: Witt, Olaf [VerfasserIn]
• Titel: Histone deacetylase 10 promotes autophagy-mediated cell survival
• Verf.angabe: Ina Oehme, Jan-Peter Linke, Barbara C. Böck, Till Milde, Marco Lodrini, Bettina Hartenstein, Inga Wiegand, Christian Eckert, Wilfried Roth, Marcel Kool, Sylvia Kaden, Hermann-Josef Gröne, Johannes H. Schulte, Sven Lindner, Anne Hamacher-Brady, Nathan R. Brady, Hedwig E. Deubzer, and Olaf Witt
• E-Jahr: 2013
• Jahr: June 25, 2013
• Umfang: 10 S.
• Fussnoten: Gesehen am 29.11.2021
• Titel Quelle: Enthalten in: National Academy of Sciences (Washington, DC)Proceedings of the National Academy of Sciences of the United States of America
• Ort Quelle: Washington, DC : National Acad. of Sciences, 1915
• Jahr Quelle: 2013
• Band/Heft Quelle: 110(2013), 28, Seite E2592-E2601
• ISSN Quelle: 1091-6490
• DOI: doi:10.1073/pnas.1300113110
• Datenträger: Online-Ressource
• Sprache: eng
• Bibliogr. Hinweis: Erscheint auch als : Druck-Ausgabe: Histone deacetylase 10 promotes autophagy-mediated cell survival. - 2013
• Sach-SW: childhood tumors
• Sach-SW: drug resistance
• Sach-SW: HDAC inhibitor
• K10plus-PPN: 1779749589

Abstract

Tumor cells activate autophagy in response to chemotherapy-induced DNA damage as a survival program to cope with metabolic stress. Here, we provide in vitro and in vivo evidence that histone deacetylase (HDAC)10 promotes autophagy-mediated survival in neuroblastoma cells. We show that both knockdown and inhibition of HDAC10 effectively disrupted autophagy associated with sensitization to cytotoxic drug treatment in a panel of highly malignant V-MYC myelocytomatosis viral-related oncogene, neuroblastoma derived-amplified neuroblastoma cell lines, in contrast to nontransformed cells. HDAC10 depletion in neuroblastoma cells interrupted autophagic flux and induced accumulation of autophagosomes, lysosomes, and a prominent substrate of the autophagic degradation pathway, p62/sequestosome 1. Enforced HDAC10 expression protected neuroblastoma cells against doxorubicin treatment through interaction with heat shock protein 70 family proteins, causing their deacetylation. Conversely, heat shock protein 70/heat shock cognate 70 was acetylated in HDAC10-depleted cells. HDAC10 expression levels in high-risk neuroblastomas correlated with autophagy in gene-set analysis and predicted treatment success in patients with advanced stage 4 neuroblastomas. Our results demonstrate that HDAC10 protects cancer cells from cytotoxic agents by mediating autophagy and identify this HDAC isozyme as a druggable regulator of advanced-stage tumor cell survival. Moreover, these results propose a promising way to considerably improve treatment response in the neuroblastoma patient subgroup with the poorest outcome.