Krupple-Like Factor 5 is a Potential Therapeutic Target and Prognostic Marker in Epithelial Ovarian Cancer.
Krupple-like factor 5
apoptosis
epithelial ovarian cancer
epithelial–mesenchymal transition
pSTAT3
Journal
Frontiers in pharmacology
ISSN: 1663-9812
Titre abrégé: Front Pharmacol
Pays: Switzerland
ID NLM: 101548923
Informations de publication
Date de publication:
2020
2020
Historique:
received:
25
08
2020
accepted:
10
11
2020
entrez:
11
1
2021
pubmed:
12
1
2021
medline:
12
1
2021
Statut:
epublish
Résumé
Epithelial ovarian cancer (EOC) is the most lethal gynecological malignancy. Despite current therapeutic and surgical options, advanced EOC shows poor prognosis. Identifying novel molecular therapeutic targets is highly needed in the management of EOC. Krupple-like factor 5 (KLF5), a zinc-finger transcriptional factor, is highly expressed in a variety of cancer types. However, its role and expression in EOC is not fully illustrated. Immunohistochemical analysis was performed to assess KLF5 protein expression in 425 primary EOC samples using tissue microarray. We also addressed the function of KLF5 in EOC and its interaction with signal transducer and activator of transcription 3 (STAT3) signaling pathway. We found that KLF5 overexpressed in 53% (229/425) of EOC samples, and is associated with aggressive markers. Forced expression of KLF5 enhanced cell growth in low expressing EOC cell line, MDAH2774. Conversely, knockdown of KLF5 reduced cell growth, migration, invasion and progression of epithelial to mesenchymal transition in KLF5 expressing cell lines, OVISE and OVSAHO. Importantly, silencing of KLF5 decreased the self-renewal ability of spheroids generated from OVISE and OVSAHO cell lines. In addition, downregulation of KLF5 potentiated the effect of cisplatin to induce apoptosis in these cell lines. These data reveals the pro-tumorigenic role of KLF5 in EOC and uncover its role in activation of STAT3 signaling pathway, suggesting the importance of KLF5 as a potential therapeutic target for EOC therapy.
Identifiants
pubmed: 33424607
doi: 10.3389/fphar.2020.598880
pii: 598880
pmc: PMC7793801
doi:
Types de publication
Journal Article
Langues
eng
Pagination
598880Informations de copyright
Copyright © 2020 Siraj, Pratheeshkumar, Divya, Parvathareddy, Alobaisi, Thangavel,Siraj, Al-Badawi, Al-Dayel and Al-Kuraya.
Déclaration de conflit d'intérêts
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
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