2019
Šimečková, Šárka; Kahounová, Zuzana; Fedr, Radek; Remšík, Ján; Slabáková, Eva; Suchánková, Tereza; Procházková, Jiřina; Bouchal, Jan; Kharaishvili, Gvantsa; Král, Milan; Beneš, Petr; Souček, Karel
High Skp2 expression is associated with a mesenchymal phenotype and increased tumorigenic potential of prostate cancer cells. Journal Article
In: Scientific reports, vol. 9, no. 1, pp. 5695, 2019, ISSN: 2045-2322, (Place: England).
Abstract | Links | BibTeX | Tags: *Epithelial-Mesenchymal Transition, *Gene Expression Regulation, Animals, CD24 Antigen/genetics, Cell Line, Humans, Hyaluronan Receptors/genetics, Male, Mice, Neoplasm Grading, Neoplastic, Neoplastic Stem Cells/metabolism/*physiology, Nude, PC-3 Cells, Prostatic Neoplasms/*genetics/metabolism/physiopathology, S-Phase Kinase-Associated Proteins/*genetics, Tumor, Xenograft Model Antitumor Assays
@article{simeckova_high_2019,
title = {High Skp2 expression is associated with a mesenchymal phenotype and increased tumorigenic potential of prostate cancer cells.},
author = {Šárka Šimečková and Zuzana Kahounová and Radek Fedr and Ján Remšík and Eva Slabáková and Tereza Suchánková and Jiřina Procházková and Jan Bouchal and Gvantsa Kharaishvili and Milan Král and Petr Beneš and Karel Souček},
doi = {10.1038/s41598-019-42131-y},
issn = {2045-2322},
year = {2019},
date = {2019-04-01},
journal = {Scientific reports},
volume = {9},
number = {1},
pages = {5695},
abstract = {Skp2 is a crucial component of SCF(Skp2) 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.},
note = {Place: England},
keywords = {*Epithelial-Mesenchymal Transition, *Gene Expression Regulation, Animals, CD24 Antigen/genetics, Cell Line, Humans, Hyaluronan Receptors/genetics, Male, Mice, Neoplasm Grading, Neoplastic, Neoplastic Stem Cells/metabolism/*physiology, Nude, PC-3 Cells, Prostatic Neoplasms/*genetics/metabolism/physiopathology, S-Phase Kinase-Associated Proteins/*genetics, Tumor, Xenograft Model Antitumor Assays},
pubstate = {published},
tppubtype = {article}
}
Skp2 is a crucial component of SCF(Skp2) 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.