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HDAC9 promotes glioblastoma growth via TAZ-mediated EGFR pathway activation.

Yang R, Wu Y, Wang M, Sun Z, Zou J, Zhang Y, Cui H - Oncotarget (2015)

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: State Key Laboratory of Silkworm Genome Biology, Southwest University, Chongqing 400715, P.R. China.

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.

No MeSH data available.


Related in: MedlinePlus

Knockdown of HDAC9 inhibits the activity of the EGFR/AKT/ERK pathway(A) The expression of p-EGFR, EGFR, p-AKT, AKT, p-ERK1/2 and ERK1/2 in HDAC9-knockdown U87 cells was measured by western blot assay. (B) Representative blots showing the expression of p-EGFR, EGFR, p-AKT, AKT, p-ERK1/2 and ERK1/2 in HDAC9-knockdown LN229 cells. (C) The expression of p-EGFR, EGFR, p-AKT, AKT, p-ERK1/2 and ERK1/2 in tumor xenografts was measured by western blot.
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Figure 5: Knockdown of HDAC9 inhibits the activity of the EGFR/AKT/ERK pathway(A) The expression of p-EGFR, EGFR, p-AKT, AKT, p-ERK1/2 and ERK1/2 in HDAC9-knockdown U87 cells was measured by western blot assay. (B) Representative blots showing the expression of p-EGFR, EGFR, p-AKT, AKT, p-ERK1/2 and ERK1/2 in HDAC9-knockdown LN229 cells. (C) The expression of p-EGFR, EGFR, p-AKT, AKT, p-ERK1/2 and ERK1/2 in tumor xenografts was measured by western blot.

Mentions: Some studies have demonstrated that activation of the epidermal growth factor receptor (EGFR) could accelerate cell cycle progression by activating the cyclin E-CDK2 kinase, and then promote cell proliferation. EGFR is a crucial signaling molecule, and PI3K/AKT and Ras-ERK are important downstream signaling pathways of EGFR. Therefore, the expression of p-EGFR, p-AKT and p-ERK1/2 proteins was measured by western blot assay in HDAC9-knockdown and shGFP GBM cells. Representative blots for U87 and LN229 cells are shown in Figure 5A and 5B. To test whether the expression of HDAC9 is also associated with EGFR signaling in vivo, the expression of the p-EGFR, p-AKT and p-ERK1/2 proteins was examined in the xenograft tumor tissues formed by HDAC9-knockdown U87 cells (Figure 5C). The expression of these proteins in HDAC9-knockdown cells and in the tumor tissues formed by the HDAC9-knockdown U87 cells was all markedly reduced compared with their controls. All these results suggested that the HDAC9-promoted proliferation and tumor formation of GBM cells were possibly mediated by potentiating the EGFR signaling pathway.


HDAC9 promotes glioblastoma growth via TAZ-mediated EGFR pathway activation.

Yang R, Wu Y, Wang M, Sun Z, Zou J, Zhang Y, Cui H - Oncotarget (2015)

Knockdown of HDAC9 inhibits the activity of the EGFR/AKT/ERK pathway(A) The expression of p-EGFR, EGFR, p-AKT, AKT, p-ERK1/2 and ERK1/2 in HDAC9-knockdown U87 cells was measured by western blot assay. (B) Representative blots showing the expression of p-EGFR, EGFR, p-AKT, AKT, p-ERK1/2 and ERK1/2 in HDAC9-knockdown LN229 cells. (C) The expression of p-EGFR, EGFR, p-AKT, AKT, p-ERK1/2 and ERK1/2 in tumor xenografts was measured by western blot.
© Copyright Policy - open-access
Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC4480706&req=5

Figure 5: Knockdown of HDAC9 inhibits the activity of the EGFR/AKT/ERK pathway(A) The expression of p-EGFR, EGFR, p-AKT, AKT, p-ERK1/2 and ERK1/2 in HDAC9-knockdown U87 cells was measured by western blot assay. (B) Representative blots showing the expression of p-EGFR, EGFR, p-AKT, AKT, p-ERK1/2 and ERK1/2 in HDAC9-knockdown LN229 cells. (C) The expression of p-EGFR, EGFR, p-AKT, AKT, p-ERK1/2 and ERK1/2 in tumor xenografts was measured by western blot.
Mentions: Some studies have demonstrated that activation of the epidermal growth factor receptor (EGFR) could accelerate cell cycle progression by activating the cyclin E-CDK2 kinase, and then promote cell proliferation. EGFR is a crucial signaling molecule, and PI3K/AKT and Ras-ERK are important downstream signaling pathways of EGFR. Therefore, the expression of p-EGFR, p-AKT and p-ERK1/2 proteins was measured by western blot assay in HDAC9-knockdown and shGFP GBM cells. Representative blots for U87 and LN229 cells are shown in Figure 5A and 5B. To test whether the expression of HDAC9 is also associated with EGFR signaling in vivo, the expression of the p-EGFR, p-AKT and p-ERK1/2 proteins was examined in the xenograft tumor tissues formed by HDAC9-knockdown U87 cells (Figure 5C). The expression of these proteins in HDAC9-knockdown cells and in the tumor tissues formed by the HDAC9-knockdown U87 cells was all markedly reduced compared with their controls. All these results suggested that the HDAC9-promoted proliferation and tumor formation of GBM cells were possibly mediated by potentiating the EGFR signaling pathway.

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: State Key Laboratory of Silkworm Genome Biology, Southwest University, Chongqing 400715, P.R. China.

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.

No MeSH data available.


Related in: MedlinePlus