YAP promotes autophagy and progression of gliomas via upregulating HMGB1
Abstract Background Due to the hypoxia and nutrient deficiency microenvironment, glioblastoma (GBM) exhibits high autophagy activity and autophagy plays an important role in the progression of GBM. However, the molecular mechanism of autophagy in GBM progression remains unclear. The aim of this stud...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2021-03-01
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| Series: | Journal of Experimental & Clinical Cancer Research |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s13046-021-01897-8 |
| _version_ | 1818721542336413696 |
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| author | Min Zhao Yu Zhang Yang Jiang Kai Wang Xiang Wang Ding Zhou Yan Wang Rutong Yu Xiuping Zhou |
| author_facet | Min Zhao Yu Zhang Yang Jiang Kai Wang Xiang Wang Ding Zhou Yan Wang Rutong Yu Xiuping Zhou |
| author_sort | Min Zhao |
| collection | DOAJ |
| description | Abstract Background Due to the hypoxia and nutrient deficiency microenvironment, glioblastoma (GBM) exhibits high autophagy activity and autophagy plays an important role in the progression of GBM. However, the molecular mechanism of autophagy in GBM progression remains unclear. The aim of this study is to delve out the role and mechanism of yes-associated protein (YAP) in GBM autophagy and progression. Methods The level of autophagy or autophagy flux were assessed by using western blotting, GFP-LC3 puncta (Live) imaging, transmission electron microscopy and GFP-RFP-LC3 assay. The GBM progression was detected by using CCK8, EdU, nude mouse xenograft and Ki67 staining. Isobaric tags for relative and absolute quantification (iTraq) quantitative proteomics was used to find out the mediator of YAP in autophagy. Expression levels of YAP and HMGB1 in tissue samples from GBM patients were examined by Western blotting, tissue microarray and immunohistochemistry. Results YAP over-expression enhanced glioma cell autophagy under basal and induced conditions. In addition, blocking autophagy by chloroquine abolished the promoting effect of YAP on glioma growth. Mechanistically, YAP over-expression promoted the transcription and translocation of high mobility group box 1(HMGB1), a well-known regulator of autophagy, from nucleus to cytoplasm. Down-regulation of HMGB1 abolished the promoting effect of YAP on autophagy and glioma growth. Furthermore, the expression of YAP and HMGB1 were positively associated with each other and suggested poor prognosis for clinical GBM. Conclusion YAP promoted glioma progression by enhancing HMGB1-mediated autophagy, indicating that YAP-HMGB1 axis was a feasible therapeutic target for GBM. Our study revealed a clinical opportunity involving the combination of chemo-radiotherapy with pharmacological autophagy inhibition for treating GBM patients with YAP high expression. |
| first_indexed | 2024-12-17T20:40:23Z |
| format | Article |
| id | doaj.art-9c3037b44ba9441db11801b06da48048 |
| institution | Directory Open Access Journal |
| issn | 1756-9966 |
| language | English |
| last_indexed | 2024-12-17T20:40:23Z |
| publishDate | 2021-03-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Experimental & Clinical Cancer Research |
| spelling | doaj.art-9c3037b44ba9441db11801b06da480482022-12-21T21:33:19ZengBMCJournal of Experimental & Clinical Cancer Research1756-99662021-03-0140111510.1186/s13046-021-01897-8YAP promotes autophagy and progression of gliomas via upregulating HMGB1Min Zhao0Yu Zhang1Yang Jiang2Kai Wang3Xiang Wang4Ding Zhou5Yan Wang6Rutong Yu7Xiuping Zhou8Institute of Nervous System Diseases, Xuzhou Medical UniversityInstitute of Nervous System Diseases, Xuzhou Medical UniversityInstitute of Nervous System Diseases, Xuzhou Medical UniversityInstitute of Nervous System Diseases, Xuzhou Medical UniversityInstitute of Nervous System Diseases, Xuzhou Medical UniversityInstitute of Nervous System Diseases, Xuzhou Medical UniversityInstitute of Nervous System Diseases, Xuzhou Medical UniversityInstitute of Nervous System Diseases, Xuzhou Medical UniversityInstitute of Nervous System Diseases, Xuzhou Medical UniversityAbstract Background Due to the hypoxia and nutrient deficiency microenvironment, glioblastoma (GBM) exhibits high autophagy activity and autophagy plays an important role in the progression of GBM. However, the molecular mechanism of autophagy in GBM progression remains unclear. The aim of this study is to delve out the role and mechanism of yes-associated protein (YAP) in GBM autophagy and progression. Methods The level of autophagy or autophagy flux were assessed by using western blotting, GFP-LC3 puncta (Live) imaging, transmission electron microscopy and GFP-RFP-LC3 assay. The GBM progression was detected by using CCK8, EdU, nude mouse xenograft and Ki67 staining. Isobaric tags for relative and absolute quantification (iTraq) quantitative proteomics was used to find out the mediator of YAP in autophagy. Expression levels of YAP and HMGB1 in tissue samples from GBM patients were examined by Western blotting, tissue microarray and immunohistochemistry. Results YAP over-expression enhanced glioma cell autophagy under basal and induced conditions. In addition, blocking autophagy by chloroquine abolished the promoting effect of YAP on glioma growth. Mechanistically, YAP over-expression promoted the transcription and translocation of high mobility group box 1(HMGB1), a well-known regulator of autophagy, from nucleus to cytoplasm. Down-regulation of HMGB1 abolished the promoting effect of YAP on autophagy and glioma growth. Furthermore, the expression of YAP and HMGB1 were positively associated with each other and suggested poor prognosis for clinical GBM. Conclusion YAP promoted glioma progression by enhancing HMGB1-mediated autophagy, indicating that YAP-HMGB1 axis was a feasible therapeutic target for GBM. Our study revealed a clinical opportunity involving the combination of chemo-radiotherapy with pharmacological autophagy inhibition for treating GBM patients with YAP high expression.https://doi.org/10.1186/s13046-021-01897-8GliomaYAPAutophagyHMGB1Progression |
| spellingShingle | Min Zhao Yu Zhang Yang Jiang Kai Wang Xiang Wang Ding Zhou Yan Wang Rutong Yu Xiuping Zhou YAP promotes autophagy and progression of gliomas via upregulating HMGB1 Journal of Experimental & Clinical Cancer Research Glioma YAP Autophagy HMGB1 Progression |
| title | YAP promotes autophagy and progression of gliomas via upregulating HMGB1 |
| title_full | YAP promotes autophagy and progression of gliomas via upregulating HMGB1 |
| title_fullStr | YAP promotes autophagy and progression of gliomas via upregulating HMGB1 |
| title_full_unstemmed | YAP promotes autophagy and progression of gliomas via upregulating HMGB1 |
| title_short | YAP promotes autophagy and progression of gliomas via upregulating HMGB1 |
| title_sort | yap promotes autophagy and progression of gliomas via upregulating hmgb1 |
| topic | Glioma YAP Autophagy HMGB1 Progression |
| url | https://doi.org/10.1186/s13046-021-01897-8 |
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