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Updated: Nov 9, 2025

Evaluating the Angiogenetic Properties of Ovarian Cancer Stem-Like Cells using the Three-Dimensional Co-Culture System, NICO-1
Published on: December 5, 2020
Niclosamide's potential direct targets in ovarian cancer†
Nikola Sekulovski1, James A MacLean1,2, Sambasiva R Bheemireddy3
1Department of Physiology, Southern Illinois University School of Medicine, Carbondale, IL, USA.
Abstract:
Recent evidence indicates that niclosamide is an anti-cancer compound that is able to inhibit several signaling pathways. Although niclosamide has previously been identified by high-throughput screening platforms as a potential effective compound against several cancer types, no direct binding interactions with distinct biological molecule(s) has been established. The present study identifies key signal transduction mechanisms altered by niclosamide in ovarian cancer. Using affinity purification with a biotin-modified niclosamide derivative and mass spectrometry analysis, several RNA-binding proteins (RBPs) were identified. We chose the two RBPs, FXR1 and IGF2BP2, for further analysis. A significant correlation exists in which high-expression of FXR1 or IGF2BP2 is associated with reduced survival of ovarian cancer patients. Knockdown of FXR1 or IGF2BP2 in ovarian cancer cells resulted in significantly reduced cell viability, adhesion, and migration. Furthermore, FXR1 or IGF2BP2 deficient ovarian cancer cells exhibited reduced response to most doses of niclosamide showing greater cell viability than those with intact RBPs. These results suggest that FXR1 and IGF2BP2 are direct targets of niclosamide and could have critical activities that drive multiple oncogenic pathways in ovarian cancer.
Insights
Niclosamide, an anti-cancer drug, targets RNA-binding proteins FXR1 and IGF2BP2 in ovarian cancer. Inhibiting these proteins reduces cancer cell survival and migration, suggesting they are key drivers of oncogenic pathways.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Niclosamide is recognized as an anti-cancer agent with potential against various cancer types.
- Previous research identified niclosamide's efficacy through high-throughput screening, but direct molecular targets remained elusive.
- Understanding niclosamide's precise mechanisms in ovarian cancer is crucial for therapeutic development.
Purpose of the Study:
- To identify the direct molecular targets of niclosamide in ovarian cancer.
- To elucidate the role of identified targets in ovarian cancer progression and response to niclosamide.
- To investigate the involvement of specific RNA-binding proteins (RBPs) in niclosamide's anti-cancer effects.
Main Methods:
- Affinity purification using a biotin-modified niclosamide derivative followed by mass spectrometry to identify binding proteins.
- Selection and further analysis of identified RNA-binding proteins (RBPs), specifically FXR1 and IGF2BP2.
- Ovarian cancer cell line experiments involving gene knockdown and assessment of cell viability, adhesion, migration, and drug response.
Main Results:
- Several RNA-binding proteins (RBPs) were identified as potential direct binding partners of niclosamide.
- High expression of FXR1 and IGF2BP2 correlates with reduced survival in ovarian cancer patients.
- Knockdown of FXR1 or IGF2BP2 significantly decreased ovarian cancer cell viability, adhesion, and migration, and reduced niclosamide efficacy.
Conclusions:
- FXR1 and IGF2BP2 are identified as direct targets of niclosamide in ovarian cancer.
- These RBPs play critical roles in driving multiple oncogenic pathways in ovarian cancer.
- Targeting FXR1 and IGF2BP2 may represent a novel therapeutic strategy for ovarian cancer treatment.
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