ArticleOncogene2016
Gankyrin facilitates follicle-stimulating hormone-driven ovarian cancer cell proliferation through the PI3K/AKT/HIF-1α/cyclin D1 pathway.
Article in Oncogene, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 60 papers.
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Who cites it
60 citing papers in PubMed, 102 citations in OpenAlex.
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- Introgression drives adaptation to the plateau environment in a subterranean rodent.BMC biology · 2024Article
- TSLP enhances progestin response in endometrial cancer via androgen receptor signal pathway.British journal of cancer · 2024Article
- ANGPTL4 regulates ovarian cancer progression by activating the ERK1/2 pathway.Cancer cell international · 2024Article
- Targeting the FSH/FSHR axis in ovarian cancer: advanced treatment using nanotechnology and immunotherapy.Frontiers in endocrinology · 2024Review
- A Photoactivated Ru (II) Polypyridine Complex Induced Oncotic Necrosis of A549 Cells by Activating Oxidative Phosphorylation and Inhibiting DNA Synthesis as Revealed by Quantitative Proteomics.International journal of molecular sciences · 2023Article
- β Cell and Autophagy: What Do We Know?Biomolecules · 2023Review
- Roles of hypoxia-inducible factor in hepatocellular carcinoma under local ablation therapies.Frontiers in pharmacology · 2023Review
- Hormone supply to the pituitary gland: A comprehensive investigation of female‑related tumors (Review).International journal of molecular medicine · 2022Review
- Gankyrin modulated non-small cell lung cancer progression via glycolysis metabolism in a YAP1-dependent manner.Cell death discovery · 2022Article
- Vitamin DCell biology and toxicology · 2022Article
- Action Sites and Clinical Application of HIF-1α Inhibitors.Molecules (Basel, Switzerland) · 2022Review
- Identification of key genes associated with polycystic ovary syndrome (PCOS) and ovarian cancer using an integrated bioinformatics analysis.Journal of ovarian research · 2022Article
- Qing Zao Fang (QZF) Alleviates the Inflammatory Microenvironment of the Submandibular Gland in Sjögren's Syndrome Based on the PI3K/Akt/HIF-1Disease markers · 2022Article
- Repressing phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit gamma by microRNA-142-3p restrains the progression of hepatocellular carcinoma.Bioengineered · 2022Article
- Reprogramming Carbohydrate Metabolism in Cancer and Its Role in Regulating the Tumor Microenvironment.Sub-cellular biochemistry · 2022Article
Corrections and comments
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Authors and funding
16 authors at 7 institutions in 2 countries.
Funding
Abstract
Gankyrin is a regulatory subunit of the 26kD proteasome complex. As a novel oncoprotein, gankyrin is expressed aberrantly in cancers from several different sites and has been shown to contribute to oncogenesis in endometrial and cervical carcinomas. Neither gankyrin's contribution to the development of epithelial ovarian cancer nor its interaction with follicle-stimulating hormone (FSH)-driven proliferation in ovarian cancer has been studied. Here we have found that gankyrin is overexpressed in ovarian cancers compared with benign ovarian cystadenomas and that gankyrin regulates FSH upregulation of cyclin D1. Importantly, gankyrin regulates PI3K/AKT signaling by downregulating PTEN. Prolonged AKT activation by FSH stimulation of the FSH receptor (FSHR) promotes gankyrin expression, which, in turn, enhances AKT activation by inhibiting PTEN. Overexpression of gankyrin decreases hypoxia inducible factor-1α (HIF-1α) protein levels, but has little effect on HIF-1α mRNA levels, which could be attributed to gankyrin mediating HIF-1α protein stability via the ubiquitin-proteasome pathway. Reduction in HIF-1α protein stability led to attenuation of the binding with cyclin D1 promoter, resulted in abolishment of the negative regulation of cyclin D1 by HIF-1α, which promotes proliferation of ovarian cancer cells. Our results document that gankyrin regulates HIF-1α protein stability and cyclin D1 expression, ultimately mediating FSH-driven ovarian cancer cell proliferation.
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