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Epigenetic downregulation of STAT6 increases HIF-1alpha expression via mTOR/S6K/S6, leading to enhanced hypoxic viability of glioma cells

Authors
Park, SJ  | Kim, H  | Kim, SH  | Joe, EH  | Jou, I
Citation
Acta neuropathologica communications, 7(1). : 149-149, 2019
Journal Title
Acta neuropathologica communications
ISSN
2051-5960
Abstract
Multifunctional signal transducer and activator of transcription (STAT) proteins play important roles in cancer. Here, we have shown that STAT6 is epigenetically silenced in some cases of malignant glioblastoma, which facilitates cancer cell survival in a hypoxic microenvironment. This downregulation results from hypermethylation of CpG islands within the STAT6 promoter by DNA methyltransferases. STAT6 interacts with Rheb under hypoxia and inhibits mTOR/S6K/S6 signaling, in turn, inducing increased HIF-1alpha translation. STAT6 silencing and consequent tumor-promoting effects are additionally observed in glioma stem-like cells (GSC). Despite recent advances in cancer treatment, survival rates have shown little improvement. This is particularly true in the case of glioma, where multimodal treatment and precision medicine is needed. Our study supports the application of epigenetic restoration of STAT6 with the aid of DNA methyltransferase inhibitors, such as 5-aza-2-deoxycytidine, for treatment of STAT6-silenced gliomas.
Keywords
MeSH

DOI
10.1186/s40478-019-0798-z
PMID
31530290
Appears in Collections:
Journal Papers > Research Organization > Inflamm-aging Translational Research Center
Journal Papers > School of Medicine / Graduate School of Medicine > Pharmacology
Journal Papers > School of Medicine / Graduate School of Medicine > Neurosurgery
Ajou Authors
김, 세혁  |  김, 현미  |  박, 수정  |  조, 은혜  |  주, 일로
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