High Skp2 expression is associated with a mesenchymal phenotype and increased tumorigenic potential of prostate cancer cells

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F68081707%3A_____%2F19%3A00504487" target="_blank" >RIV/68081707:_____/19:00504487 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/00159816:_____/19:00071081 RIV/00216224:14310/19:00109767 RIV/61989592:15110/19:73598293 RIV/00098892:_____/19:N0000082 RIV/00027162:_____/19:N0000067

Výsledek na webu

<a href="https://www.nature.com/articles/s41598-019-42131-y.pdf" target="_blank" >https://www.nature.com/articles/s41598-019-42131-y.pdf</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1038/s41598-019-42131-y" target="_blank" >10.1038/s41598-019-42131-y</a>

Jazyk výsledku

angličtina

Název v původním jazyce

High Skp2 expression is associated with a mesenchymal phenotype and increased tumorigenic potential of prostate cancer cells

Popis výsledku v původním jazyce

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.

Název v anglickém jazyce

High Skp2 expression is associated with a mesenchymal phenotype and increased tumorigenic potential of prostate cancer cells

Popis výsledku anglicky

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.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

40401 - Agricultural biotechnology and food biotechnology

Projekt

Výsledek vznikl pri realizaci vícero projektů. Více informací v záložce Projekty.

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2019

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Scientific Reports

ISSN

2045-2322

e-ISSN

—

Svazek periodika

9

Číslo periodika v rámci svazku

APR 5 2019

Stát vydavatele periodika

GB - Spojené království Velké Británie a Severního Irska

Počet stran výsledku

10

Strana od-do

5695

Kód UT WoS článku

000463482800035

EID výsledku v databázi Scopus

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