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Article

Transgelin Contributes to a Poor Response of Metastatic Renal Cell Carcinoma to Sunitinib Treatment

1
Department of Biochemistry, Faculty of Science, Masaryk University, 625 00 Brno, Czech Republic
2
Proteomics Core Facility, Central European Institute of Technology, Masaryk University, 625 00 Brno, Czech Republic
3
Department of Comprehensive Cancer Care, Masaryk Memorial Cancer Institute, 656 53 Brno, Czech Republic
4
Department of Comprehensive Cancer Care, Faculty of Medicine, Masaryk University, 656 53 Brno, Czech Republic
*
Author to whom correspondence should be addressed.
Academic Editors: Paola Bendinelli and Paola Maroni
Biomedicines 2021, 9(9), 1145; https://doi.org/10.3390/biomedicines9091145
Received: 28 July 2021 / Revised: 20 August 2021 / Accepted: 24 August 2021 / Published: 3 September 2021
(This article belongs to the Special Issue Molecular Mechanisms of Bone Metastases in Biomedicines)
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. View Full-Text
Keywords: mccRCC; sunitinib; resistance; DIA-MS; transgelin mccRCC; sunitinib; resistance; DIA-MS; transgelin
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MDPI and ACS Style

Bouchalova, P.; Beranek, J.; Lapcik, P.; Potesil, D.; Podhorec, J.; Poprach, A.; Bouchal, P. Transgelin Contributes to a Poor Response of Metastatic Renal Cell Carcinoma to Sunitinib Treatment. Biomedicines 2021, 9, 1145. https://doi.org/10.3390/biomedicines9091145

AMA Style

Bouchalova P, Beranek J, Lapcik P, Potesil D, Podhorec J, Poprach A, Bouchal P. Transgelin Contributes to a Poor Response of Metastatic Renal Cell Carcinoma to Sunitinib Treatment. Biomedicines. 2021; 9(9):1145. https://doi.org/10.3390/biomedicines9091145

Chicago/Turabian Style

Bouchalova, Pavla, Jindrich Beranek, Petr Lapcik, David Potesil, Jan Podhorec, Alexandr Poprach, and Pavel Bouchal. 2021. "Transgelin Contributes to a Poor Response of Metastatic Renal Cell Carcinoma to Sunitinib Treatment" Biomedicines 9, no. 9: 1145. https://doi.org/10.3390/biomedicines9091145

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