Abstract
Histone deacetylase 9 (HDAC9), a member of class II HDACs, regulates a wide variety of normal and abnormal physiological functions. We found that HDAC9 is over-expressed in prognostically poor glioblastoma patients. Knockdown HDAC9 decreased proliferation in vitro and tumor formation in vivo. HDAC9 accelerated cell cycle in part by potentiating the EGFR signaling pathway. Also, HDAC9 interacted with TAZ, a key downstream effector of Hippo pathway. Knockdown of HDAC9 decreased the expression of TAZ. We found that overexpressed TAZ in HDAC9-knockdown cells abrogated the effects induced by HDAC9 silencing both in vitro and in vivo. We demonstrated that HDAC9 promotes tumor formation of glioblastoma via TAZ-mediated EGFR pathway activation, and provide the evidence for promising target for the treatment of glioblastoma.
Keywords:
EGFR; HDAC9; TAZ; cell cycle; glioblastoma.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Cell Cycle
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Cell Line, Tumor
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Cell Proliferation / physiology
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ErbB Receptors / metabolism*
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Female
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Glioblastoma / genetics
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Glioblastoma / metabolism*
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Glioblastoma / pathology*
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Heterografts
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Histone Deacetylases / genetics
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Histone Deacetylases / metabolism*
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Humans
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Intracellular Signaling Peptides and Proteins / metabolism*
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Mice
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Mice, SCID
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Prognosis
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Repressor Proteins / genetics
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Repressor Proteins / metabolism*
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Signal Transduction
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Trans-Activators
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Transcription Factors
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Transcriptional Coactivator with PDZ-Binding Motif Proteins
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Xenograft Model Antitumor Assays
Substances
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Intracellular Signaling Peptides and Proteins
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Repressor Proteins
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Trans-Activators
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Transcription Factors
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Transcriptional Coactivator with PDZ-Binding Motif Proteins
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WWTR1 protein, human
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EGFR protein, human
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ErbB Receptors
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HDAC9 protein, human
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Histone Deacetylases