ArticleCancers2021
A Novel ZIP4-HDAC4-VEGFA Axis in High-Grade Serous Ovarian Cancer.
Article in Cancers, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
10 citing papers in PubMed, 13 citations in OpenAlex.
- Prokaryotic expression of the giant panda VEGFA gene and the preparation and characterization of its monoclonal antibodies.Veterinary and animal science · 2026Article
- Prognostic and Predictive Significance of Cancer Stem Cell Markers (ZIP-4 and ALDH1A1) in Ovarian Serous Carcinoma Patients: An Immunohistochemical Study.Asian Pacific journal of cancer prevention : APJCP · 2026Article
- The SLC-ome of membrane transport: From molecular discovery to physiology and clinical applications.Physiological reviews · 2025Review
- Cancer 3D Models: Essential Tools for Understanding and Overcoming Drug Resistance.Oncology research · 2025Review
- Article
- ZIP4: a promising early diagnostic and therapeutic targets for pancreatic cancer.American journal of cancer research · 2024Review
- Immunotherapeutic Approaches in Ovarian Cancer.Current issues in molecular biology · 2023Review
- HDAC4 in cancer: A multitasking platform to drive not only epigenetic modifications.Frontiers in molecular biosciences · 2023Review
- Targeting HIF-1α by Natural and Synthetic Compounds: A Promising Approach for Anti-Cancer Therapeutics Development.Molecules (Basel, Switzerland) · 2022Review
- PreclinicalFrontiers in endocrinology · 2022Article
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
We have recently identified ZIP4 as a novel cancer stem cell (CSC) marker in high-grade serous ovarian cancer (HGSOC). While it converts drug-resistance to cisplatin (CDDP), we unexpectedly found that ZIP4 induced sensitization of HGSOC cells to histone deacetylase inhibitors (HDACis). Mechanistically, ZIP4 selectively upregulated HDAC IIa HDACs, with little or no effect on HDACs in other classes. HDAC4 knockdown (KD) and LMK-235 inhibited spheroid formation in vitro and tumorigenesis in vivo, with hypoxia inducible factor-1 alpha (HIF1α) and endothelial growth factor A (VEGFA) as functional downstream mediators of HDAC4. Moreover, we found that ZIP4, HDAC4, and HIF1α were involved in regulating secreted VEGFA in HGSOC cells. Furthermore, we tested our hypothesis that co-targeting CSC via the ZIP4-HDAC4 axis and non-CSC using CDDP is necessary and highly effective by comparing the effects of ZIP4-knockout/KD, HDAC4-KD, and HDACis, in the presence or absence of CDDP on tumorigenesis in mouse models. Our results showed that the co-targeting strategy was highly effective. Finally, data from human HGSOC tissues showed that ZIP4 and HDAC4 were upregulated in a subset of recurrent tumors, justifying the clinical relevance of the study. In summary, our study provides a new mechanistic-based targeting strategy for HGSOC.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.