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Silence of Hippo Pathway Associates with Pro-Tumoral Immunosuppression: Potential Therapeutic Target of Glioblastomas

Authors
 Eui Hyun Kim  ;  Bo Hwa Sohn  ;  Young-Gyu Eun  ;  Dong Jin Lee  ;  Sun Young Yim  ;  Seok-Gu Kang  ;  Ju-Seog Lee 
Citation
 CELLS, Vol.9(8) : 1761, 2020-06 
Journal Title
CELLS(Cells)
ISSN
 2073-4409 
Issue Date
2020-06
Keywords
Hippo pathway ; M2 polarization ; glioblastoma ; immune checkpoint ; immune signature ; macrophage
Abstract
The critical role of the Hippo pathway has been recently investigated in various cancers, but little is known about its role in glioblastoma (GBM). In order to evaluate the clinical relevance of the Hippo pathway in GBM, we generated a core gene expression signature from four different previously-established silence of Hippo pathway (SOH) signatures. Based on a newly generated core SOH signature, a SOH and active Hippo pathway (AH) was predicted in GBM samples from The Cancer Genome Atlas (TCGA) and validated in a separate cohort. A comparative analysis was performed on multi-panel genomic datasets from TCGA and the possible association of SOH with immune activity and epithelial mesenchymal transition was also evaluated. The SOH signature was associated with poor prognosis in GBM in both cohorts. Expression levels of CTGF and CYR61, the most reliable and well-known downstream targets of YAP1, were markedly increased in the SOH subgroup of GBM patients. SOH signature was strongly associated with a high immune signature score and mesenchymal features. Genes differentially expressed between SOH and AH groups revealed many markers for inhibitory immune checkpoints and M2-polarized macrophages were upregulated in the SOH subgroup, suggesting that SOH may induce the resistance of cancer cells to host immune response in GBM. In summary, SOH is significantly associated with the poor prognosis of GBM patients and is possibly mediated by pro-tumoral immunosuppression.
Files in This Item:
T202004962.pdf Download
DOI
10.3390/cells9081761
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Neurosurgery (신경외과학교실) > 1. Journal Papers
Yonsei Authors
Kang, Seok Gu(강석구) ORCID logo https://orcid.org/0000-0001-5676-2037
Kim, Eui Hyun(김의현) ORCID logo https://orcid.org/0000-0002-2523-7122
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/180604
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