ArticleOncogene2008
HIF alpha expression in VHL-deficient renal cancer cells is dependent on phospholipase D.
Article in Oncogene, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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Who cites it
39 citing papers in PubMed, 62 citations in OpenAlex.
- Essential role of PLD2 in hypoxia-induced stemness and therapy resistance in ovarian tumors.Journal of experimental & clinical cancer research : CR · 2024Article
- NADH elevation during chronic hypoxia leads to VHL-mediated HIF-1α degradation via SIRT1 inhibition.Cell & bioscience · 2023Article
- Phospholipase Family Enzymes in Lung Cancer: Looking for Novel Therapeutic Approaches.Cancers · 2023Review
- Hypoxic microenvironment in cancer: molecular mechanisms and therapeutic interventions.Signal transduction and targeted therapy · 2023Review
- TGF‑β1 affects the renal cancer miRNome and regulates tumor cells proliferation.International journal of molecular medicine · 2022Article
- Review
- PI3K/AKT/mTOR signalling pathway involvement in renal cell carcinoma pathogenesis (Review).Experimental and therapeutic medicine · 2021Review
- Hypoxia induced changes in miRNAs and their target mRNAs in extracellular vesicles of esophageal squamous cancer cells.Thoracic cancer · 2020Article
- Esophageal Microenvironment: From Precursor Microenvironment to Premetastatic Niche.Cancer management and research · 2020Review
- High Expression of PhospholipaseD2 Induced by Hypoxia Promotes Proliferation of Colon Cancer Cells through Activating NF- κ Bp65 Signaling Pathway.Pathology oncology research : POR · 2020Article
- Fatty acids - from energy substrates to key regulators of cell survival, proliferation and effector function.Cell stress · 2019Review
- Proliferative and metastatic roles for Phospholipase D in mouse models of cancer.Advances in biological regulation · 2018Review
- Phospholipase D and Its Essential Role in Cancer.Molecules and cells · 2017Review
- AQP3 small interfering RNA and PLD2 small interfering RNA inhibit the proliferation and promote the apoptosis of squamous cell carcinoma.Molecular medicine reports · 2017Article
- Emerging roles of lipid metabolism in cancer metastasis.Molecular cancer · 2017Review
- Combination of mTOR and MAPK Inhibitors-A Potential Way to Treat Renal Cell Carcinoma.Medical sciences (Basel, Switzerland) · 2016Review
- Inhibition of phospholipaseD2 increases hypoxia-induced human colon cancer cell apoptosis through inactivating of the PI3K/AKT signaling pathway.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2016Article
- Essential role for SphK1/S1P signaling to regulate hypoxia-inducible factor 2α expression and activity in cancer.Oncogenesis · 2016Article
- Physiological and pathophysiological roles for phospholipase D.Journal of lipid research · 2015Review
- Phospholipase D2 promotes degradation of hypoxia-inducible factor-1α independent of lipase activity.Experimental & molecular medicine · 2015Article
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 2 countries.
Funding
Abstract
Loss of the von Hippel-Lindau (VHL) tumor suppressor gene contributes to proliferative disorders including renal cell carcinoma. The consequence of VHL loss is increased levels of hypoxia-inducible factor-alpha (HIFalpha), which is targeted for proteolytic degradation by the VHL gene product pVHL. HIF is a transcription factor that increases the expression of factors critical for tumorigenesis in renal cell carcinoma. We report here another regulatory component of HIFalpha expression in renal cancer cells. Phospholipase D (PLD), which is commonly elevated in renal and other cancers, is required for elevated levels of both HIF1alpha and HIF2alpha in VHL-deficient renal cancer cells. The induction of both HIF1alpha and HIF2alpha by hypoxic mimetic conditions was also dependent on PLD in renal cancer cells with restored pVHL expression. The effect of PLD activity upon HIFalpha expression was at the level of translation. PLD activity also provides a survival signal that suppresses apoptosis induced by serum deprivation in the renal cancer cells. Suppression of HIF2alpha has been shown to reverse tumorigenesis with renal cancer cells. The finding here that HIF2alpha expression is dependent on PLD in renal cancer cells suggests that targeting PLD signals may represent an alternative therapeutic strategy for targeting HIF2alpha in renal cancers where HIF2alpha is critical for tumorigenesis and elevated PLD activity is common.
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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 OpenQuestion graph.