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EIF5A2 enhances stemness of epithelial ovarian cancer cells via a E2F1/KLF4 axis

Overview of attention for article published in Stem Cell Research & Therapy, March 2021
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Title
EIF5A2 enhances stemness of epithelial ovarian cancer cells via a E2F1/KLF4 axis
Published in
Stem Cell Research & Therapy, March 2021
DOI 10.1186/s13287-021-02256-2
Pubmed ID
Authors

Kun Wang, Yiyang Wang, Yuanjian Wang, Shujie Liu, Chunyan Wang, Shuo Zhang, Tianli Zhang, Xingsheng Yang

Abstract

Ovarian cancer stem cells (OCSC), endowed with tumor-initiating and self-renewal capacity, would account not only for the tumor growth, the peritoneal metastasis, and the relapse, but also for the acquisition of chemotherapy resistance. Nevertheless, figuring out their phenotypical and functional traits has proven quite challenging, mainly because of the heterogeneity of ovarian cancer. A deeper understanding of OCSC mechanisms will shed light on the development of the disease. Therefore, we aim to explore it for the design of innovative treatment regimens which aim at the eradication of ovarian cancer through the elimination of the CSC component. In this study, immunohistochemistry assay and western blot assay were used to detect protein expression in the primary tumor and peritoneal multi-cellular aggregates/spheroids (MCAs/MCSs). OCSCs induced from cell line SKOV3 and HO-8910 were enriched in a serum-free medium (SFM). The effect of EIF5A2 on CSC-like properties was detected by sphere-forming assays, re-differentiation assays, quantitative real-time polymerase chain reaction, western blotting, flow cytometry, cell viability assays, immunofluorescence staining, and in vivo xenograft experiments. RNA-sequencing (RNA-seq) was used to reveal the mechanism by which EIF5A2 positively modulates the stem-like properties of ovarian cancer cells. Expression of EIF5A2 was significantly higher in peritoneal MCAs/MCSs compared to matched primary tumors, and EIF5A2 was also unregulated in ovarian cancer cell line-derived spheroids. Knockdown of EIF5A2 reduced the expression of the stem-related markers (ALDH1A1 and OCT-4), inhibited self-renewal ability, improved the sensitivity to chemotherapeutic drugs, and inhibited tumorigenesis in vivo. Mechanistic studies revealed that EIF5A2 knockdown reduced the expression of KLF4, which could partially rescue stem-like properties abolished by EIF5A2 knockdown or strengthened by EIF5A2 overexpression, through the transcription factor E2F1, which directly bind to KLF4 promoter. Our results imply that EIF5A2 positively regulates stemness in ovarian cancer cells via E2F1/KLF4 pathway and may serve as a potential target in CSCs-targeted therapy for ovarian cancer.

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Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 13 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 13 100%

Demographic breakdown

Readers by professional status Count As %
Researcher 3 23%
Student > Doctoral Student 1 8%
Student > Master 1 8%
Unknown 8 62%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 2 15%
Medicine and Dentistry 2 15%
Immunology and Microbiology 1 8%
Unknown 8 62%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 17 March 2021.
All research outputs
#20,692,340
of 23,289,753 outputs
Outputs from Stem Cell Research & Therapy
#2,093
of 2,453 outputs
Outputs of similar age
#363,775
of 426,106 outputs
Outputs of similar age from Stem Cell Research & Therapy
#95
of 113 outputs
Altmetric has tracked 23,289,753 research outputs across all sources so far. This one is in the 1st percentile – i.e., 1% of other outputs scored the same or lower than it.
So far Altmetric has tracked 2,453 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 5.1. This one is in the 1st percentile – i.e., 1% of its peers scored the same or lower than it.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 426,106 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 1st percentile – i.e., 1% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 113 others from the same source and published within six weeks on either side of this one. This one is in the 1st percentile – i.e., 1% of its contemporaries scored the same or lower than it.