Histone deacetylase 6 promotes growth of glioblastoma through the MKK7/JNK/c-Jun signaling pathway

Journal of Neurochemistry
Ziyan HuangZhongmin Yuan

Abstract

Histone deacetylase 6 (HDAC6) activity contributes to the malignant proliferation, invasion, and migration of glioma cells (GCs), but the molecular mechanisms underlying the processes remains elusive. Here, we reported that HDAC6 inhibition by Ricolinostat (ACY-1215) or CAY10603 led to a remarkable decrease in the phosphorylation of c-Jun N-terminal kinase (JNK) and c-Jun, which preceded its suppressive effects on glioma cell growth. Further investigation showed that these effects resulted from HDAC6 inhibitor-induced suppression of MAPK kinase 7 (MKK7), which was identified to be critical for JNK activation and exerts the oncogenic roles in GCs. Selectively silencing HDAC6 by siRNAs had the same responses, whereas transient transfections expressing HDAC6 promoted MKK7 expression. Interestingly, by performing Q-PCR, HDAC6 inhibition did not cause a down-regulation of MKK7 mRNA level, whereas the suppressive effects on MKK7 protein can be efficiently blocked by the proteasomal inhibitor MG132. As a further test, elevating MKK7-JNK activity was sufficient to rescue HDAC6 inhibitor-mediated-suppressive effects on c-Jun activation and the malignant features. The suppression of both MKK7 expression and JNK/c-Jun activities was invol...Continue Reading

References

Jan 16, 1999·Molecular and Cellular Biology·C TournierR J Davis
Dec 17, 2009·The Journal of Biological Chemistry·Ying WuWei Zhang
Mar 3, 2011·Journal of Cellular and Molecular Medicine·Jacob E ShabasonKevin Camphausen
Oct 5, 2013·Molecular Cancer Therapeutics·Andrea NewboldRicky W Johnstone
Nov 20, 2013·Journal of Pharmacology & Pharmacotherapeutics·Jaykaran Charan, N D Kantharia
Apr 18, 2014·Nature Reviews. Neuroscience·Eleanor T Coffey
Nov 22, 2014·Journal of Medicinal Chemistry·Pierre KochStefan A Laufer
Jan 27, 2015·Molecular & Cellular Proteomics : MCP·Rommel A MathiasIleana M Cristea
Jan 1, 2014·Cell & Bioscience·Eva BaxterJason S Lee
Aug 19, 2015·Journal of Clinical Immunology·Tiphanie P VogelMegan A Cooper
Oct 29, 2015·Journal of Neuroscience Research·Vimal PandeyPhanithi Prakash Babu
Nov 3, 2015·The Journal of Clinical Investigation·Hiroshi NakashimaE Antonio Chiocca
Jan 1, 2015·Oncolytic Virotherapy·Hiroshi NakashimaEnnio Antonio Chiocca
Jan 6, 2017·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Dan T VoglSagar Lonial
Jan 19, 2017·Oncotarget·Dong Hoon LeeSo Hee Kwon
Sep 18, 2017·Breast Cancer Research and Treatment·Roisin M ConnollySaraswati Sukumar
Sep 25, 2017·Cell Chemical Biology·Scott RibichRobert A Copeland
Feb 27, 2018·European Journal of Pharmacology·Maria Domenica Sanna, Nicoletta Galeotti
May 31, 2018·Open Medicine·Changjiang Yin, Pibao Li
Jul 20, 2018·Nature Reviews. Immunology·Wilfried Ellmeier, Christian Seiser
Sep 12, 2018·Journal of Cellular Physiology·Samantha S RomanickBradley S Ferguson
Oct 16, 2018·British Journal of Cancer·Maciej KaliszczakEric O Aboagye
Oct 18, 2018·Clinical and Translational Medicine·Debarati GhoshSonali Bhattacharjee

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Citations

Jan 19, 2020·Clinical & Translational Oncology : Official Publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico·X WangX Zhu
Oct 30, 2020·Frontiers in Cell and Developmental Biology·Monica PhimmachanhDavid R Croucher
Nov 5, 2020·Pharmacology & Therapeutics·Elena KunadisChristina Piperi

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