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

J 2021

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

BOUCHALOVÁ, Pavla, Jindřich BERÁNEK, Petr LAPČÍK, David POTĚŠIL, Ján PODHOREC et. al.

Základní údaje

Originální název

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

Název česky

Transgelin přispívá ke slabé odpovědi metastatického renálního karcinomu na léčbu sunitinibem

Autoři

BOUCHALOVÁ, Pavla (203 Česká republika, domácí), Jindřich BERÁNEK (203 Česká republika, domácí), Petr LAPČÍK (203 Česká republika, domácí), David POTĚŠIL (203 Česká republika, domácí), Ján PODHOREC (703 Slovensko, domácí), Alexandr POPRACH (203 Česká republika, domácí) a Pavel BOUCHAL (203 Česká republika, garant, domácí)

Vydání

Biomedicines, Basel, MDPI, 2021, 2227-9059

Další údaje

Jazyk

angličtina

Typ výsledku

Článek v odborném periodiku

Obor

10608 Biochemistry and molecular biology

Stát vydavatele

Švýcarsko

Utajení

není předmětem státního či obchodního tajemství

Odkazy

URL

Impakt faktor

Impact factor: 4.757

Kód RIV

RIV/00216224:14310/21:00120144

Organizační jednotka

Přírodovědecká fakulta

DOI

http://dx.doi.org/10.3390/biomedicines9091145

UT WoS

000699070400001

Klíčová slova anglicky

mccRCC; sunitinib; resistance; DIA-MS; transgelin

Štítky

14110811, podil, rivok

Příznaky

Mezinárodní význam, Recenzováno

Změněno: 28. 2. 2022 08:12, Mgr. Marie Šípková, DiS.

Anotace

V originále

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.

Návaznosti

NV19-08-00250, projekt VaV

Název: Proteotypová klasifikace renálního karcinomu ve vztahu k prognóze a terapeutické odpovědi

Investor: Ministerstvo zdravotnictví ČR, Proteotypová klasifikace renálního karcinomu ve vztahu k prognóze a terapeutické odpovědi

Citovat

BOUCHALOVÁ, Pavla, Jindřich BERÁNEK, Petr LAPČÍK, David POTĚŠIL, Ján PODHOREC, Alexandr POPRACH a Pavel BOUCHAL. Transgelin Contributes to a Poor Response of Metastatic Renal Cell Carcinoma to Sunitinib Treatment. Biomedicines. Basel: MDPI, 2021, roč. 9, č. 9, s. 1145-1163. ISSN 2227-9059. Dostupné z: https://dx.doi.org/10.3390/biomedicines9091145.

@article{1795618,
   author = {Bouchalová, Pavla and Beránek, Jindřich and Lapčík, Petr and Potěšil, David and Podhorec, Ján and Poprach, Alexandr and Bouchal, Pavel},
   article_location = {Basel},
   article_number = {9},
   doi = {http://dx.doi.org/10.3390/biomedicines9091145},
   keywords = {mccRCC; sunitinib; resistance; DIA-MS; transgelin},
   language = {eng},
   issn = {2227-9059},
   journal = {Biomedicines},
   title = {Transgelin Contributes to a Poor Response of Metastatic Renal Cell Carcinoma to Sunitinib Treatment},
   url = {https://www.mdpi.com/2227-9059/9/9/1145},
   volume = {9},
   year = {2021}
}

TY  - JOUR
ID  - 1795618
AU  - Bouchalová, Pavla - Beránek, Jindřich - Lapčík, Petr - Potěšil, David - Podhorec, Ján - Poprach, Alexandr - Bouchal, Pavel
PY  - 2021
TI  - Transgelin Contributes to a Poor Response of Metastatic Renal Cell Carcinoma to Sunitinib Treatment
JF  - Biomedicines
VL  - 9
IS  - 9
SP  - 1145
EP  - 1145
PB  - MDPI
SN  - 22279059
KW  - mccRCC
KW  - sunitinib
KW  - resistance
KW  - DIA-MS
KW  - transgelin
UR  - https://www.mdpi.com/2227-9059/9/9/1145
N2  - 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.
ER  -

BOUCHALOVÁ, Pavla, Jindřich BERÁNEK, Petr LAPČÍK, David POTĚŠIL, Ján PODHOREC, Alexandr POPRACH a Pavel BOUCHAL. Transgelin Contributes to a Poor Response of Metastatic Renal Cell Carcinoma to Sunitinib Treatment. \textit{Biomedicines}. Basel: MDPI, 2021, roč.~9, č.~9, s.~1145-1163. ISSN~2227-9059. Dostupné z: https://dx.doi.org/10.3390/biomedicines9091145.

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