Quantitative proteomics reveals reduction of endocytic machinery components in gliomasResearch in context
Background: Gliomas are the most frequent and aggressive malignancies of the central nervous system. Decades of molecular analyses have demonstrated that gliomas accumulate genetic alterations that culminate in enhanced activity of receptor tyrosine kinases and downstream mediators. While the geneti...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2019-08-01
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| Series: | EBioMedicine |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2352396419304815 |
| _version_ | 1819148162185560064 |
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| author | Dominik P. Buser Marie-Françoise Ritz Suzette Moes Cristobal Tostado Stephan Frank Martin Spiess Luigi Mariani Paul Jenö Jean-Louis Boulay Gregor Hutter |
| author_facet | Dominik P. Buser Marie-Françoise Ritz Suzette Moes Cristobal Tostado Stephan Frank Martin Spiess Luigi Mariani Paul Jenö Jean-Louis Boulay Gregor Hutter |
| author_sort | Dominik P. Buser |
| collection | DOAJ |
| description | Background: Gliomas are the most frequent and aggressive malignancies of the central nervous system. Decades of molecular analyses have demonstrated that gliomas accumulate genetic alterations that culminate in enhanced activity of receptor tyrosine kinases and downstream mediators. While the genetic alterations, like gene amplification or loss, have been well characterized, little information exists about changes in the proteome of gliomas of different grades. Methods: We performed unbiased quantitative proteomics of human glioma biopsies by mass spectrometry followed by bioinformatic analysis. Findings: Various pathways were found to be up- or downregulated. In particular, endocytosis as pathway was affected by a vast and concomitant reduction of multiple machinery components involved in initiation, formation, and scission of endocytic carriers. Both clathrin-dependent and -independent endocytosis were changed, since not only clathrin, AP-2 adaptins, and endophilins were downregulated, but also dynamin that is shared by both pathways. The reduction of endocytic machinery components caused increased receptor cell surface levels, a prominent phenotype of defective endocytosis. Analysis of additional biopsies revealed that depletion of endocytic machinery components was a common trait of various glioma grades and subclasses. Interpretation: We propose that impaired endocytosis creates a selective advantage in glioma tumor progression due to prolonged receptor tyrosine kinase signaling from the cell surface. Fund: This work was supported by Grants 316030-164105 (to P. Jenö), 31003A-162643 (to M. Spiess) and PP00P3-176974 (to G. Hutter) from the Swiss National Science Foundation. Further funding was received by the Department of Surgery from the University Hospital Basel. Keywords: Glioma, Endocytosis, RTK, Dynamin, Clathrin, AP-2 |
| first_indexed | 2024-12-22T13:41:19Z |
| format | Article |
| id | doaj.art-20bc9908e8084d0fb3d1c346b7b87f13 |
| institution | Directory Open Access Journal |
| issn | 2352-3964 |
| language | English |
| last_indexed | 2024-12-22T13:41:19Z |
| publishDate | 2019-08-01 |
| publisher | Elsevier |
| record_format | Article |
| series | EBioMedicine |
| spelling | doaj.art-20bc9908e8084d0fb3d1c346b7b87f132022-12-21T18:23:55ZengElsevierEBioMedicine2352-39642019-08-01463241Quantitative proteomics reveals reduction of endocytic machinery components in gliomasResearch in contextDominik P. Buser0Marie-Françoise Ritz1Suzette Moes2Cristobal Tostado3Stephan Frank4Martin Spiess5Luigi Mariani6Paul Jenö7Jean-Louis Boulay8Gregor Hutter9Biozentrum, University of Basel, CH-4056 Basel, Switzerland; Corresponding authors at: Klingelbergstrasse 50/70, CH-4056 Basel, Switzerland.Brain Tumor Biology and Immunotherapy group, Department of Biomedicine, University Hospital Basel, University of Basel, CH-4031 Basel, SwitzerlandProteomics Core Facility, Biozentrum, University of Basel, CH-4056 Basel, SwitzerlandBrain Tumor Biology and Immunotherapy group, Department of Biomedicine, University Hospital Basel, University of Basel, CH-4031 Basel, SwitzerlandInstitute of Pathology, University Hospital Basel, CH-4031 Basel, SwitzerlandBiozentrum, University of Basel, CH-4056 Basel, SwitzerlandBrain Tumor Biology and Immunotherapy group, Department of Biomedicine, University Hospital Basel, University of Basel, CH-4031 Basel, Switzerland; Department of Neurosurgery, University Hospital Basel, CH-4031 Basel, SwitzerlandProteomics Core Facility, Biozentrum, University of Basel, CH-4056 Basel, Switzerland; Corresponding authors at: Klingelbergstrasse 50/70, CH-4056 Basel, Switzerland.Brain Tumor Biology and Immunotherapy group, Department of Biomedicine, University Hospital Basel, University of Basel, CH-4031 Basel, Switzerland; Corresponding authors at: Hebelstrasse 20, CH-4031 Basel, Switzerland.Brain Tumor Biology and Immunotherapy group, Department of Biomedicine, University Hospital Basel, University of Basel, CH-4031 Basel, Switzerland; Department of Neurosurgery, University Hospital Basel, CH-4031 Basel, Switzerland; Corresponding authors at: Hebelstrasse 20, CH-4031 Basel, Switzerland.Background: Gliomas are the most frequent and aggressive malignancies of the central nervous system. Decades of molecular analyses have demonstrated that gliomas accumulate genetic alterations that culminate in enhanced activity of receptor tyrosine kinases and downstream mediators. While the genetic alterations, like gene amplification or loss, have been well characterized, little information exists about changes in the proteome of gliomas of different grades. Methods: We performed unbiased quantitative proteomics of human glioma biopsies by mass spectrometry followed by bioinformatic analysis. Findings: Various pathways were found to be up- or downregulated. In particular, endocytosis as pathway was affected by a vast and concomitant reduction of multiple machinery components involved in initiation, formation, and scission of endocytic carriers. Both clathrin-dependent and -independent endocytosis were changed, since not only clathrin, AP-2 adaptins, and endophilins were downregulated, but also dynamin that is shared by both pathways. The reduction of endocytic machinery components caused increased receptor cell surface levels, a prominent phenotype of defective endocytosis. Analysis of additional biopsies revealed that depletion of endocytic machinery components was a common trait of various glioma grades and subclasses. Interpretation: We propose that impaired endocytosis creates a selective advantage in glioma tumor progression due to prolonged receptor tyrosine kinase signaling from the cell surface. Fund: This work was supported by Grants 316030-164105 (to P. Jenö), 31003A-162643 (to M. Spiess) and PP00P3-176974 (to G. Hutter) from the Swiss National Science Foundation. Further funding was received by the Department of Surgery from the University Hospital Basel. Keywords: Glioma, Endocytosis, RTK, Dynamin, Clathrin, AP-2http://www.sciencedirect.com/science/article/pii/S2352396419304815 |
| spellingShingle | Dominik P. Buser Marie-Françoise Ritz Suzette Moes Cristobal Tostado Stephan Frank Martin Spiess Luigi Mariani Paul Jenö Jean-Louis Boulay Gregor Hutter Quantitative proteomics reveals reduction of endocytic machinery components in gliomasResearch in context EBioMedicine |
| title | Quantitative proteomics reveals reduction of endocytic machinery components in gliomasResearch in context |
| title_full | Quantitative proteomics reveals reduction of endocytic machinery components in gliomasResearch in context |
| title_fullStr | Quantitative proteomics reveals reduction of endocytic machinery components in gliomasResearch in context |
| title_full_unstemmed | Quantitative proteomics reveals reduction of endocytic machinery components in gliomasResearch in context |
| title_short | Quantitative proteomics reveals reduction of endocytic machinery components in gliomasResearch in context |
| title_sort | quantitative proteomics reveals reduction of endocytic machinery components in gliomasresearch in context |
| url | http://www.sciencedirect.com/science/article/pii/S2352396419304815 |
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