ArticleBritish journal of cancer2011
Factor inhibiting HIF (FIH-1) promotes renal cancer cell survival by protecting cells from HIF-1α-mediated apoptosis.
Article in British journal of cancer, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 40 citations in OpenAlex.
- Deficiency of factor-inhibiting HIF creates a tumor-promoting immune microenvironment.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Factor-inhibiting HIF (FIH) promotes lung cancer progression.JCI insight · 2023Article
- Oxygen-Sensing Protein Cysteamine Dioxygenase from Mandarin Fish Involved in the Arg/N-Degron Pathway andViruses · 2023Article
- Novel Drugs with High Efficacy against Tumor Angiogenesis.International journal of molecular sciences · 2022Review
- No Time to Die: How Kidney Cancer Evades Cell Death.International journal of molecular sciences · 2022Review
- hZIP1 Inhibits Progression of Clear Cell Renal Cell Carcinoma by Suppressing NF-kB/HIF-1α Pathway.Frontiers in oncology · 2021Article
- Beyond glycolysis: Hypoxia signaling as a master regulator of alternative metabolic pathways and the implications in clear cell renal cell carcinoma.Cancer letters · 2020Review
- Gankyrin is a novel biomarker for disease progression and prognosis of patients with renal cell carcinoma.EBioMedicine · 2019Article
- Ascorbate modulates the hypoxic pathway by increasing intracellular activity of the HIF hydroxylases in renal cell carcinoma cells.Hypoxia (Auckland, N.Z.) · 2019Article
- Regulation of Tumor Progression by Programmed Necrosis.Oxidative medicine and cellular longevity · 2018Review
- HIF-1α induction during reperfusion avoids maladaptive repair after renal ischemia/reperfusion involving miR127-3p.Scientific reports · 2017Article
- Regulation of the hypoxic tumor environment in hepatocellular carcinoma using RNA interference.Cancer cell international · 2017Review
- Hypoxic regulation of the noncoding genome and NEAT1.Briefings in functional genomics · 2016Review
- Hypoxia, Hypoxia-inducible Transcription Factors, and Renal Cancer.European urology · 2016Review
- Repression of hypoxia-inducible factor α signaling by Set7-mediated methylation.Nucleic acids research · 2015Article
- Genetic modification of hypoxia signaling in animal models and its effect on cancer.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2015Review
- miR-31 is consistently inactivated in EBV-associated nasopharyngeal carcinoma and contributes to its tumorigenesis.Molecular cancer · 2014Article
- Current views on cell metabolism in SDHx-related pheochromocytoma and paraganglioma.Endocrine-related cancer · 2014Review
- EAF2 suppresses hypoxia-induced factor 1α transcriptional activity by disrupting its interaction with coactivator CBP/p300.Molecular and cellular biology · 2014Article
- The roles of Jumonji-type oxygenases in human disease.Epigenomics · 2014Review
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Authors and funding
9 authors at 2 institutions in 2 countries.
Funding
Abstract
backgroundClear cell renal cell carcinoma (CCRCC) is the commonest form of kidney cancer. Up to 91% have biallelic inactivation of VHL, resulting in stabilisation of HIF-α subunits. Factor inhibiting HIF-1 is an enzyme that hydroxylates HIF-α subunits and prevents recruitment of the co-activator CBP/P300. An important question is whether FIH-1 controls HIF activity in CCRCC.
methodsHuman VHL defective CCRCC lines RCC10, RCC4 and 786-O were used to determine the role of FIH-1 in modulating HIF activity, using small interfering RNA knockdown, retroviral gene expression, quantitative RT-PCR, western blot analysis, Annexin V and propidium iodide labelling.
resultsAlthough it was previously suggested that FIH-1 is suppressed in CCRCC, we found that FIH-1 mRNA and protein are actually present at similar levels in CCRCC and normal kidney. The FIH-1 inhibition or knockdown in the VHL defective CCRCC lines RCC10 and RCC4 (which express both HIF-1α and HIF-2α) resulted in increased expression of HIF target genes. In the 786-O CCRCC cell line, which expresses only HIF-2α, FIH-1 attenuation showed no significant effect on expression of these genes; introduction of HIF-1α resulted in sensitivity of HIF targets to FIH-1 knockdown. In RCC4 and RCC10, knockdown of FIH-1 increased apoptosis. Suppressing HIF-1α expression in RCC10 prevented FIH-1 knockdown from increasing apoptosis.
conclusionOur results support a unifying model in which HIF-1α has a tumour suppressor action in CCRCC, held in check by FIH-1. Inhibiting FIH-1 in CCRCC could be used to bias the HIF response towards HIF-1α and decrease tumour cell viability.
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