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High Skp2 expression is associated with a mesenchymal phenotype and increased tumorigenic potential of prostate cancer cells
Š. Šimečková, Z. Kahounová, R. Fedr, J. Remšík, E. Slabáková, T. Suchánková, J. Procházková, J. Bouchal, G. Kharaishvili, M. Král, P. Beneš, K. Souček,
Language English Country Great Britain
Document type Journal Article, Research Support, Non-U.S. Gov't
Grant support
NV15-28628A
MZ0
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Digital library NLK
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- MeSH
- CD24 Antigen genetics MeSH
- Hyaluronan Receptors genetics MeSH
- PC-3 Cells MeSH
- Epithelial-Mesenchymal Transition * MeSH
- Humans MeSH
- Mice, Nude MeSH
- Mice MeSH
- Cell Line, Tumor MeSH
- Neoplastic Stem Cells metabolism physiology MeSH
- Prostatic Neoplasms genetics metabolism physiopathology MeSH
- S-Phase Kinase-Associated Proteins genetics MeSH
- Gene Expression Regulation, Neoplastic * MeSH
- Neoplasm Grading MeSH
- Xenograft Model Antitumor Assays MeSH
- Animals MeSH
- Check Tag
- Humans MeSH
- Male MeSH
- Mice MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
Skp2 is a crucial component of SCFSkp2 E3 ubiquitin ligase and is often overexpressed in various types of cancer, including prostate cancer (PCa). The epithelial-to-mesenchymal transition (EMT) is involved in PCa progression. The acquisition of a mesenchymal phenotype that results in a cancer stem cell (CSC) phenotype in PCa was described. Therefore, we aimed to investigate the expression and localization of Skp2 in clinical samples from patients with PCa, the association of Skp2 with EMT status, and the role of Skp2 in prostate CSC. We found that nuclear expression of Skp2 was increased in patients with PCa compared to those with benign hyperplasia, and correlated with high Gleason score in PCa patients. Increased Skp2 expression was observed in PCa cell lines with mesenchymal and CSC-like phenotype compared to their epithelial counterparts. Conversely, the CSC-like phenotype was diminished in cells in which SKP2 expression was silenced. Furthermore, we observed that Skp2 downregulation led to the decrease in subpopulation of CD44+CD24- cancer stem-like cells. Finally, we showed that high expression levels of both CD24 and CD44 were associated with favorable recurrence-free survival for PCa patients. This study uncovered the Skp2-mediated CSC-like phenotype with oncogenic functions in PCa.
Department of Chemistry and Toxicology Veterinary Research Institute Brno Czech Republic
Department of Urology University Hospital Olomouc Czech Republic
References provided by Crossref.org
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- $a Šimečková, Šárka $u Department of Cytokinetics, Institute of Biophysics of the Czech Academy of Sciences, Brno, Czech Republic. Center of Biomolecular and Cellular Engineering, International Clinical Research Center, St. Anne´s University Hospital Brno, Brno, Czech Republic. Department of Experimental Biology, Faculty of Science, Masaryk University, Brno, Czech Republic.
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- $a High Skp2 expression is associated with a mesenchymal phenotype and increased tumorigenic potential of prostate cancer cells / $c Š. Šimečková, Z. Kahounová, R. Fedr, J. Remšík, E. Slabáková, T. Suchánková, J. Procházková, J. Bouchal, G. Kharaishvili, M. Král, P. Beneš, K. Souček,
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- $a Skp2 is a crucial component of SCFSkp2 E3 ubiquitin ligase and is often overexpressed in various types of cancer, including prostate cancer (PCa). The epithelial-to-mesenchymal transition (EMT) is involved in PCa progression. The acquisition of a mesenchymal phenotype that results in a cancer stem cell (CSC) phenotype in PCa was described. Therefore, we aimed to investigate the expression and localization of Skp2 in clinical samples from patients with PCa, the association of Skp2 with EMT status, and the role of Skp2 in prostate CSC. We found that nuclear expression of Skp2 was increased in patients with PCa compared to those with benign hyperplasia, and correlated with high Gleason score in PCa patients. Increased Skp2 expression was observed in PCa cell lines with mesenchymal and CSC-like phenotype compared to their epithelial counterparts. Conversely, the CSC-like phenotype was diminished in cells in which SKP2 expression was silenced. Furthermore, we observed that Skp2 downregulation led to the decrease in subpopulation of CD44+CD24- cancer stem-like cells. Finally, we showed that high expression levels of both CD24 and CD44 were associated with favorable recurrence-free survival for PCa patients. This study uncovered the Skp2-mediated CSC-like phenotype with oncogenic functions in PCa.
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- $a Kahounová, Zuzana $u Department of Cytokinetics, Institute of Biophysics of the Czech Academy of Sciences, Brno, Czech Republic. Center of Biomolecular and Cellular Engineering, International Clinical Research Center, St. Anne´s University Hospital Brno, Brno, Czech Republic.
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- $a Fedr, Radek $u Department of Cytokinetics, Institute of Biophysics of the Czech Academy of Sciences, Brno, Czech Republic. Center of Biomolecular and Cellular Engineering, International Clinical Research Center, St. Anne´s University Hospital Brno, Brno, Czech Republic.
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- $a Remšík, Ján $u Department of Cytokinetics, Institute of Biophysics of the Czech Academy of Sciences, Brno, Czech Republic. Center of Biomolecular and Cellular Engineering, International Clinical Research Center, St. Anne´s University Hospital Brno, Brno, Czech Republic. Department of Experimental Biology, Faculty of Science, Masaryk University, Brno, Czech Republic. Human Oncology & Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, New York, 10065, USA.
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- $a Souček, Karel $u Department of Cytokinetics, Institute of Biophysics of the Czech Academy of Sciences, Brno, Czech Republic. ksoucek@ibp.cz. Center of Biomolecular and Cellular Engineering, International Clinical Research Center, St. Anne´s University Hospital Brno, Brno, Czech Republic. ksoucek@ibp.cz.
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