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Title 

14-3-3β depletion drives a senescence program in glioblastoma cells through the ERK/SKP2/p27 pathway

Authors 

S B SeoJ J LeeH H YunC N ImYong Sam KimJeong Heon KoJ H Lee

Publisher 

Humana Press

Issue Date 

2018

Citation 

Molecular Neurobiology

Keywords 

14-3-3βERKGlioblastomaSenescence

Abstract 

The induction of senescence in cancer cells has recently been implicated as a mechanism of tumor regression in response to various modes of stress. 14-3-3 proteins are conserved scaffolding molecules that are involved in various cellular functions. Among the seven isoforms, 14-3-3β is specifically expressed in astrocytoma in correlation with the malignancy grade. We investigated the possible role of 14-3-3β in the regulation of senescence induction in A172 glioblastoma cells. The knockdown of 14-3-3β by specific small interfering RNA resulted in a significant change in cellular phenotypes and an increase in cells staining positive for senescence-associated β-galactosidase. Western blotting of the 14-3-3β-depleted A172 cells revealed increased p27 expression and decreased SKP2 expression, while the expression of p53 and p21 was not altered. Subsequently, we demonstrated that ERK is a key modulator of SKP2/p27 axis activity in 14-3-3β-mediated senescence based on the following: (1) 14-3-3β knockdown decreased p-ERK levels; (2) treatment with U0126, an MEK inhibitor, completely reproduced the senescence morphology as well as the expression profiles of p27 and SKP2; and (3) the senescence phenotypes induced by 14-3-3β depletion were considerably recovered by constitutively active ERK expression. Our results indicate that 14-3-3β negatively regulates senescence in glioblastoma cells via the ERK/SKP2/p27 pathway. Furthermore, 14-3-3β depletion also resulted in senescence phenotypes in U87 glioblastoma cells, suggesting that 14-3-3β could be targeted to induce premature senescence as a therapeutic strategy against glioblastoma progression

ISSN 

0893-7648

Link 

http://dx.doi.org/10.1007/s12035-017-0407-8

Appears in Collections

1. Journal Articles > Journal Articles

Registered Date

2019-05-02


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