Silence of Hippo Pathway Associates with Pro-Tumoral Immunosuppression: Potential Therapeutic Target of Glioblastomas
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-es...
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MDPI AG
2020-07-01
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| Online Access: | https://www.mdpi.com/2073-4409/9/8/1761 |
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| author | Eui Hyun Kim Bo Hwa Sohn Young-Gyu Eun Dong Jin Lee Sun Young Yim Seok-Gu Kang Ju-Seog Lee |
| author_facet | Eui Hyun Kim Bo Hwa Sohn Young-Gyu Eun Dong Jin Lee Sun Young Yim Seok-Gu Kang Ju-Seog Lee |
| author_sort | Eui Hyun Kim |
| collection | DOAJ |
| description | 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 <i>CTGF</i> and <i>CYR61</i>, the most reliable and well-known downstream targets of <i>YAP1</i>, 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. |
| first_indexed | 2024-03-10T18:17:13Z |
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| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-10T18:17:13Z |
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| spelling | doaj.art-b23e4cf1d291485b92303a95e430ffd82023-11-20T07:38:57ZengMDPI AGCells2073-44092020-07-0198176110.3390/cells9081761Silence of Hippo Pathway Associates with Pro-Tumoral Immunosuppression: Potential Therapeutic Target of GlioblastomasEui Hyun Kim0Bo Hwa Sohn1Young-Gyu Eun2Dong Jin Lee3Sun Young Yim4Seok-Gu Kang5Ju-Seog Lee6Department of Systems Biology, Division of Cancer Medicine, Unit 950, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX 77030, USADepartment of Systems Biology, Division of Cancer Medicine, Unit 950, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX 77030, USADepartment of Systems Biology, Division of Cancer Medicine, Unit 950, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX 77030, USADepartment of Systems Biology, Division of Cancer Medicine, Unit 950, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX 77030, USADepartment of Systems Biology, Division of Cancer Medicine, Unit 950, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX 77030, USADepartment of Neurosurgery, Severance Hospital, Brain Tumor Center, Yonsei University College of Medicine, Seoul 03722, KoreaDepartment of Systems Biology, Division of Cancer Medicine, Unit 950, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX 77030, USAThe 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 <i>CTGF</i> and <i>CYR61</i>, the most reliable and well-known downstream targets of <i>YAP1</i>, 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.https://www.mdpi.com/2073-4409/9/8/1761glioblastomaHippo pathwayimmune checkpointimmune signaturemacrophageM2 polarization |
| spellingShingle | Eui Hyun Kim Bo Hwa Sohn Young-Gyu Eun Dong Jin Lee Sun Young Yim Seok-Gu Kang Ju-Seog Lee Silence of Hippo Pathway Associates with Pro-Tumoral Immunosuppression: Potential Therapeutic Target of Glioblastomas Cells glioblastoma Hippo pathway immune checkpoint immune signature macrophage M2 polarization |
| title | Silence of Hippo Pathway Associates with Pro-Tumoral Immunosuppression: Potential Therapeutic Target of Glioblastomas |
| title_full | Silence of Hippo Pathway Associates with Pro-Tumoral Immunosuppression: Potential Therapeutic Target of Glioblastomas |
| title_fullStr | Silence of Hippo Pathway Associates with Pro-Tumoral Immunosuppression: Potential Therapeutic Target of Glioblastomas |
| title_full_unstemmed | Silence of Hippo Pathway Associates with Pro-Tumoral Immunosuppression: Potential Therapeutic Target of Glioblastomas |
| title_short | Silence of Hippo Pathway Associates with Pro-Tumoral Immunosuppression: Potential Therapeutic Target of Glioblastomas |
| title_sort | silence of hippo pathway associates with pro tumoral immunosuppression potential therapeutic target of glioblastomas |
| topic | glioblastoma Hippo pathway immune checkpoint immune signature macrophage M2 polarization |
| url | https://www.mdpi.com/2073-4409/9/8/1761 |
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