Transgelin Contributes to a Poor Response of Metastatic Renal Cell Carcinoma to Sunitinib Treatment
Renal cell carcinoma (RCC) represents about 2–3% of all cancers with over 400,000 new cases per year. Sunitinib, a vascular endothelial growth factor tyrosine kinase receptor inhibitor, has been used mainly for first-line treatment of metastatic clear-cell RCC with good or intermediate prognosis. Ho...
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MDPI AG
2021-09-01
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| Series: | Biomedicines |
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| Online Access: | https://www.mdpi.com/2227-9059/9/9/1145 |
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| author | Pavla Bouchalova Jindrich Beranek Petr Lapcik David Potesil Jan Podhorec Alexandr Poprach Pavel Bouchal |
| author_facet | Pavla Bouchalova Jindrich Beranek Petr Lapcik David Potesil Jan Podhorec Alexandr Poprach Pavel Bouchal |
| author_sort | Pavla Bouchalova |
| collection | DOAJ |
| description | Renal cell carcinoma (RCC) represents about 2–3% of all cancers with over 400,000 new cases per year. Sunitinib, a vascular endothelial growth factor tyrosine kinase receptor inhibitor, has been used mainly for first-line treatment of metastatic clear-cell RCC with good or intermediate prognosis. However, about one-third of metastatic RCC patients do not respond to sunitinib, leading to disease progression. Here, we aim to find and characterize proteins associated with poor sunitinib response in a pilot proteomics study. Sixteen RCC tumors from patients responding (8) vs. non-responding (8) to sunitinib 3 months after treatment initiation were analyzed using data-independent acquisition mass spectrometry, together with their adjacent non-cancerous tissues. Proteomics analysis quantified 1996 protein groups (FDR = 0.01) and revealed 27 proteins deregulated between tumors non-responding vs. responding to sunitinib, representing a pattern of deregulated proteins potentially contributing to sunitinib resistance. Gene set enrichment analysis showed an up-regulation of epithelial-to-mesenchymal transition with transgelin as one of the most significantly abundant proteins. Transgelin expression was silenced by CRISPR/Cas9 and RNA interference, and the cells with reduced transgelin level exhibited significantly slower proliferation. Our data indicate that transgelin is an essential protein supporting RCC cell proliferation, which could contribute to intrinsic sunitinib resistance. |
| first_indexed | 2024-03-10T07:52:16Z |
| format | Article |
| id | doaj.art-5f4a174c514e4526ab6fe5e567ad82ae |
| institution | Directory Open Access Journal |
| issn | 2227-9059 |
| language | English |
| last_indexed | 2024-03-10T07:52:16Z |
| publishDate | 2021-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomedicines |
| spelling | doaj.art-5f4a174c514e4526ab6fe5e567ad82ae2023-11-22T12:07:41ZengMDPI AGBiomedicines2227-90592021-09-0199114510.3390/biomedicines9091145Transgelin Contributes to a Poor Response of Metastatic Renal Cell Carcinoma to Sunitinib TreatmentPavla Bouchalova0Jindrich Beranek1Petr Lapcik2David Potesil3Jan Podhorec4Alexandr Poprach5Pavel Bouchal6Department of Biochemistry, Faculty of Science, Masaryk University, 625 00 Brno, Czech RepublicDepartment of Biochemistry, Faculty of Science, Masaryk University, 625 00 Brno, Czech RepublicDepartment of Biochemistry, Faculty of Science, Masaryk University, 625 00 Brno, Czech RepublicProteomics Core Facility, Central European Institute of Technology, Masaryk University, 625 00 Brno, Czech RepublicDepartment of Comprehensive Cancer Care, Masaryk Memorial Cancer Institute, 656 53 Brno, Czech RepublicDepartment of Comprehensive Cancer Care, Masaryk Memorial Cancer Institute, 656 53 Brno, Czech RepublicDepartment of Biochemistry, Faculty of Science, Masaryk University, 625 00 Brno, Czech RepublicRenal cell carcinoma (RCC) represents about 2–3% of all cancers with over 400,000 new cases per year. Sunitinib, a vascular endothelial growth factor tyrosine kinase receptor inhibitor, has been used mainly for first-line treatment of metastatic clear-cell RCC with good or intermediate prognosis. However, about one-third of metastatic RCC patients do not respond to sunitinib, leading to disease progression. Here, we aim to find and characterize proteins associated with poor sunitinib response in a pilot proteomics study. Sixteen RCC tumors from patients responding (8) vs. non-responding (8) to sunitinib 3 months after treatment initiation were analyzed using data-independent acquisition mass spectrometry, together with their adjacent non-cancerous tissues. Proteomics analysis quantified 1996 protein groups (FDR = 0.01) and revealed 27 proteins deregulated between tumors non-responding vs. responding to sunitinib, representing a pattern of deregulated proteins potentially contributing to sunitinib resistance. Gene set enrichment analysis showed an up-regulation of epithelial-to-mesenchymal transition with transgelin as one of the most significantly abundant proteins. Transgelin expression was silenced by CRISPR/Cas9 and RNA interference, and the cells with reduced transgelin level exhibited significantly slower proliferation. Our data indicate that transgelin is an essential protein supporting RCC cell proliferation, which could contribute to intrinsic sunitinib resistance.https://www.mdpi.com/2227-9059/9/9/1145mccRCCsunitinibresistanceDIA-MStransgelin |
| spellingShingle | Pavla Bouchalova Jindrich Beranek Petr Lapcik David Potesil Jan Podhorec Alexandr Poprach Pavel Bouchal Transgelin Contributes to a Poor Response of Metastatic Renal Cell Carcinoma to Sunitinib Treatment Biomedicines mccRCC sunitinib resistance DIA-MS transgelin |
| title | Transgelin Contributes to a Poor Response of Metastatic Renal Cell Carcinoma to Sunitinib Treatment |
| title_full | Transgelin Contributes to a Poor Response of Metastatic Renal Cell Carcinoma to Sunitinib Treatment |
| title_fullStr | Transgelin Contributes to a Poor Response of Metastatic Renal Cell Carcinoma to Sunitinib Treatment |
| title_full_unstemmed | Transgelin Contributes to a Poor Response of Metastatic Renal Cell Carcinoma to Sunitinib Treatment |
| title_short | Transgelin Contributes to a Poor Response of Metastatic Renal Cell Carcinoma to Sunitinib Treatment |
| title_sort | transgelin contributes to a poor response of metastatic renal cell carcinoma to sunitinib treatment |
| topic | mccRCC sunitinib resistance DIA-MS transgelin |
| url | https://www.mdpi.com/2227-9059/9/9/1145 |
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