ArticleOncogene2011
Opposite functions of HIF-α isoforms in VEGF induction by TGF-β1 under non-hypoxic conditions.
Article in Oncogene, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 53 citations in OpenAlex.
- Metabolic control of smooth muscle cell phenotype switching in atherosclerosis.Science advances · 2026Article
- Dynamics simulations of hypoxia inducible factor-1 regulatory network in cancer using formal verification techniques.Frontiers in molecular biosciences · 2024Article
- Hypoxia-induced signaling in the cardiovascular system: pathogenesis and therapeutic targets.Signal transduction and targeted therapy · 2023Review
- Mechanisms of HIF-driven immunosuppression in tumour microenvironment.Journal of the Egyptian National Cancer Institute · 2023Review
- LINC00152 induced by TGF-β promotes metastasis via HuR in lung adenocarcinoma.Cell death & disease · 2022Article
- Review
- PHD2 attenuates high-glucose-induced blood retinal barrier breakdown in human retinal microvascular endothelial cells by regulating the Hif-1α/VEGF pathway.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2022Article
- Anti-Cancer Activity of Phytochemicals Targeting Hypoxia-Inducible Factor-1 Alpha.International journal of molecular sciences · 2021Review
- Gene expression profile identifies distinct molecular subtypes and potential therapeutic genes in Merkel cell carcinoma.Translational oncology · 2020Article
- Mutual Antagonism of Hypoxia-Inducible Factor Isoforms in Cardiac, Vascular, and Renal Disorders.JACC. Basic to translational science · 2020Review
- Gene expression of four targets in situ of the first trimester maternal-fetoplacental interface.Tissue & cell · 2020Article
- Glucometabolic Reprogramming in the Hepatocellular Carcinoma Microenvironment: Cause and Effect.Cancer management and research · 2020Review
- Review
- Multiple functions of HuR in urinary tumors.Journal of cancer research and clinical oncology · 2019Review
- Endothelial HIF-2α contributes to severe pulmonary hypertension due to endothelial-to-mesenchymal transition.American journal of physiology. Lung cellular and molecular physiology · 2018Article
- Augmentation of hypoxia-inducible factor-1-alpha in reinfused blood cells enhances diabetic ischemic wound closure in mice.Oncotarget · 2017Article
- A microfluidic oxygen gradient demonstrates differential activation of the hypoxia-regulated transcription factors HIF-1α and HIF-2α.Integrative biology : quantitative biosciences from nano to macro · 2017Article
- Changes in the coelomic microclimate during carbon dioxide laparoscopy: morphological and functional implications.Pleura and peritoneum · 2017Article
- The role of hypoxia-inducible factor-2 in digestive system cancers.Cell death & disease · 2015Review
- Cross regulation between hypoxia-inducible transcription factor-1α (HIF-1α) and transforming growth factor (TGF)-ß1 mediates nickel oxide nanoparticles (NiONPs)-induced pulmonary fibrosis.American journal of translational research · 2015Article
Corrections and comments
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Authors and funding
10 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Transforming growth factor (TGF)-β1 has biphasic functions in prostate tumorigenesis, having a growth-inhibitory effect in the early stages, but in the late stages promoting tumor angiogenesis and metastasis. We demonstrate here that tumor-producing TGF-β1 induces vascular endothelial growth factor (VEGF) in prostate cancer cells, and hypoxia-inducible factor (HIF)-1α and HIF-2α has opposite functions in TGF-β1 regulation of VEGF expression under non-hypoxic conditions. The promoter response of VEGF to TGF-β1 was upregulated by the transfection of HIF-2α or siHIF-1α but downregulated by HIF-1α and siHIF-2α. Both HIF-1α and HIF-2α were induced by TGF-β1 at mRNA and protein levels, however, their nuclear translocation was differentially regulated by TGF-β1, suggesting its association with their opposite effects. VEGF induction by TGF-β1 occurred in a Smad3-dependent manner, and the Smad-binding element 2 (SBE2, -992 to -986) and hypoxia response element (-975 to -968) in the VEGF promoter were required for the promoter response to TGF-β1. Smad3 cooperated with HIF-2α in TGF-β1 activation of VEGF transcription and Smad3 binding to the SBE2 site was greatly impaired by knockdown of HIF-2α expression. Moreover, the VEGF promoter response to TGF-β1 was synergistically elevated by co-transfection of Smad3 and HIF-2α but attenuated by HIF-1α in a dose-dependent manner. Additionally, TGF-β1 was found to increase the stability of VEGF transcript by facilitating the cytoplasmic translocation of a RNA-stabilizing factor HuR. Collectively, our data show that tumor-producing TGF-β1 induces VEGF at the both transcription and post-transcriptional levels through multiple routes including Smad3, HIF-2α and HuR. This study thus suggests that autocrine TGF-β1 production may contribute to tumor angiogenesis via HIF-2α signaling under non-hypoxic conditions, providing a selective growth advantage for prostate tumor cells.
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