ArticleHepatology (Baltimore, Md.)2013
Hypoxia inducible factor 2 alpha inhibits hepatocellular carcinoma growth through the transcription factor dimerization partner 3/ E2F transcription factor 1-dependent apoptotic pathway.
Article in Hepatology (Baltimore, Md.), 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 56 papers.
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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.
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Who cites it
56 citing papers in PubMed, 81 citations in OpenAlex.
- Von Hippel-Lindau disease: pathophysiological and clinical advances.Familial cancer · 2026Review
- Impeding hypoxia-driven tumor progression in hepatocellular carcinoma: clinical and pre-clinical analyses using 2D and 3D in vitro models.Biology direct · 2026Article
- HIF2α negatively regulates MYCN protein levels and promotes a low-risk noradrenergic phenotype in neuroblastoma.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Bridging Immune Evasion and Vascular Dynamics for Novel Therapeutic Frontiers in Hepatocellular Carcinoma.Cancers · 2025Review
- Transcription factor E2F4 facilitates SUMOylation to promote HCC progression through interaction with LIN9.International journal of oncology · 2024Article
- Anlotinib potentiates anti-PD1 immunotherapy via transferrin receptor-dependent CD8Clinical and translational medicine · 2024Article
- Review
- Elevated expression of HIGD1A drives hepatocellular carcinoma progression by regulating polyamine metabolism through c-Myc-ODC1 nexus.Cancer & metabolism · 2024Article
- Hypoxia-Induced Signaling in Gut and Liver Pathobiology.Annual review of pathology · 2024Review
- Review
- An Angiogenic Gene Signature for Prediction of the Prognosis and Therapeutic Responses of Hepatocellular Carcinoma.International journal of molecular sciences · 2023Article
- Inflammatory processes involved in NASH-related hepatocellular carcinoma.Bioscience reports · 2023Review
- Bioinformatics Analysis Identifies EPAS1 as a Novel Prognostic Marker Correlated with Immune Infiltration in Acute Myeloid Leukemia.Disease markers · 2023Article
- HIF and MYC signaling in adrenal neoplasms of the neural crest: implications for pediatrics.Frontiers in endocrinology · 2023Review
- Obstructive sleep apnea and the incidence and mortality of gastrointestinal cancers: a systematic review and meta-analysis of 5,120,837 participants.Journal of gastrointestinal oncology · 2022Article
- Article
- Transcriptomic Profiling of JEG-3 cells using human leiomyoma derived matrix.Biomaterials and biosystems · 2022Article
- Regulatory mechanism of HIF-1α and its role in liver diseases: a narrative review.Annals of translational medicine · 2022Review
- HIF-2α regulates proliferation, invasion, and metastasis of hepatocellular carcinoma cellsFrontiers in oncology · 2022Article
- HIF2α Activation in NASH: A New Force Pushing Toward HCC.Cellular and molecular gastroenterology and hepatology · 2022Article
Corrections and comments
- Erratum issuedCorrection.2018
Authors and funding
15 authors at 6 institutions in 2 countries.
Funding
Abstract
unlabelledHypoxia inducible factors (HIFs) are activated in many tumors and show either promoter or suppressor activity, depending on tumor cell biology and background. However, the role of HIF member HIF-2α remains unclear in hepatocellular carcinoma (HCC). Here, HIF-2α expression was measured in HCC and paired peritumoral tissues by quantitative real-time polymerase chain reaction, western blotting, and immunofluorescence assays, and the clinical significance was explored in 246 HCC patients. In cell culture, HIF-2α levels were up-regulated or down-regulated by use of expression or short hairpin RNA recombinant plasmid, respectively. Cells were analyzed by immunoblotting, chromatin immunoprecipitation coupled with microarray, coimmunoprecipitation, and immunohistochemical staining. In vivo tumor growth was analyzed in nude mice. We found that the average expression of HIF-2α was relatively low in HCC tissues, and the decreased level was associated with lower overall survival (P=0.006). High HIF-2α expression in HCC cells induced higher levels of apoptosis and expression of proapoptotic proteins and inhibited cell and tumor growth. Furthermore, HIF-2α inhibited expression of the novel target gene, transcription factor dimerization partner 3 (TFDP3). TFDP3 protein was found to bind with E2F transcription factor 1 (E2F1) and inhibit its transcriptional activity through both p53-dependent and -independent pathways. Reintroduction of TFDP3 expression reversed HIF-2α-induced apoptosis.
conclusionsData gathered from cell lines, tumorigenicity studies, and primary HCC samples demonstrate a negative role of HIF-2α in tumors, which is mediated by the TFDP3/E2F1 pathway. Our study provides evidence supporting a possible tumor-suppressor role for HIF-2α and has uncovered a mechanism that links HIF-2α to a fundamental biological regulator, E2F1.
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