Počet záznamů: 1
Skp2 and Slug Are Coexpressed in Aggressive Prostate Cancer and Inhibited by Neddylation Blockade
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SYSNO ASEP 0542798 Druh ASEP J - Článek v odborném periodiku Zařazení RIV J - Článek v odborném periodiku Poddruh J Článek ve WOS Název Skp2 and Slug Are Coexpressed in Aggressive Prostate Cancer and Inhibited by Neddylation Blockade Tvůrce(i) Míčková, A. (CZ)
Kharaishvili, G. (CZ)
Kurfurstova, D. (CZ)
Gachechiladze, M. (CZ)
Král, M. (CZ)
Vacek, Ondřej (BFU-R) ORCID
Pokryvkova, B. (CZ)
Mistrik, M. (CZ)
Souček, Karel (BFU-R) RID, ORCID
Bouchal, J. (CZ)Celkový počet autorů 10 Číslo článku 2844 Zdroj.dok. International Journal of Molecular Sciences. - : MDPI
Roč. 22, č. 6 (2021)Poč.str. 12 s. Forma vydání Online - E Jazyk dok. eng - angličtina Země vyd. CH - Švýcarsko Klíč. slova prostate cancer ; Skp2 (S-phase kinase-associated protein 2) ; Slug ; immunohistochemistry ; multiplex ; neddylation Vědní obor RIV CE - Biochemie Obor OECD Biochemistry and molecular biology CEP NV17-28518A GA MZd - Ministerstvo zdravotnictví Způsob publikování Open access Institucionální podpora BFU-R - RVO:68081707 UT WOS 000645776800001 EID SCOPUS 85102186800 DOI 10.3390/ijms22062844 Anotace Prostate cancer (PCa) is the second leading cause of cancer-related deaths in men in Western countries, and there is still an urgent need for a better understanding of PCa progression to inspire new treatment strategies. Skp2 is a substrate-recruiting component of the E3 ubiquitin ligase complex, whose activity is regulated through neddylation. Slug is a transcriptional repressor involved in the epithelial-to-mesenchymal transition, which may contribute to therapy resistance. Although Skp2 has previously been associated with a mesenchymal phenotype and prostate cancer progression, the relationship with Slug deserves further elucidation. We have previously shown that a high Gleason score (>= 8) is associated with higher Skp2 and lower E-cadherin expression. In this study, significantly increased expression of Skp2, AR, and Slug, along with E-cadherin downregulation, was observed in primary prostate cancer in patients who already had lymph node metastases. Skp2 was slightly correlated with Slug and AR in the whole cohort (Rs 0.32 and 0.37, respectively), which was enhanced for both proteins in patients with high Gleason scores (Rs 0.56 and 0.53, respectively) and, in the case of Slug, also in patients with metastasis to lymph nodes (Rs 0.56). Coexpression of Skp2 and Slug was confirmed in prostate cancer tissues by multiplex immunohistochemistry and confocal microscopy. The same relationship between these two proteins was observed in three sets of prostate epithelial cell lines (PC3, DU145, and E2) and their mesenchymal counterparts. Chemical inhibition of Skp2, but not RNA interference, modestly decreased Slug protein in PC3 and its docetaxel-resistant subline PC3 DR12. Importantly, chemical inhibition of Skp2 by MLN4924 upregulated p27 and decreased Slug expression in PC3, PC3 DR12, and LAPC4 cells. Novel treatment strategies targeting Skp2 and Slug by the neddylation blockade may be promising in advanced prostate cancer, as recently documented for other aggressive solid tumors. Pracoviště Biofyzikální ústav Kontakt Jana Poláková, polakova@ibp.cz, Tel.: 541 517 244 Rok sběru 2022 Elektronická adresa https://www.mdpi.com/1422-0067/22/6/2844
Počet záznamů: 1