ArticleOncotarget2015
HIF-2α mediates hypoxia-induced LIF expression in human colorectal cancer cells.
Article in Oncotarget, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers, 1 of them a synthesis that pooled it.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
32 citing papers in PubMed, 1 synthesis or guideline pooled it, 47 citations in OpenAlex.
- Hypoxic Signaling in Skeletal Muscle Maintenance and Regeneration: A Systematic Review.Frontiers in physiology · 2021Pooled it
- LIFe of the sugar-free party in cancer metabolism.Trends in endocrinology and metabolism: TEM · 2026Article
- Tumor-like proliferation of CCM3 knockout endothelial cells: insights from semaxinib treatment and transcriptome profiling of co-cultures.Acta neuropathologica communications · 2026Article
- Discovery of tumor antigens in renal cell carcinoma and prospects for clinical application.Frontiers in immunology · 2026Review
- Tfcp2l1 as a central integrator of hypoxia, dedifferentiation, and tumor progression.Journal of experimental & clinical cancer research : CR · 2025Review
- Article
- Significance of LIF/LIFR Signaling in the Progression of Obesity-Driven Triple-Negative Breast Cancer.Cancers · 2024Article
- Extramedullary hematopoiesis in cancer.Experimental & molecular medicine · 2024Review
- Anoxia Rapidly Induces Changes in Expression of a Large and Diverse Set of Genes in Endothelial Cells.International journal of molecular sciences · 2023Article
- Targeting LIF/LIFR signaling in cancer.Genes & diseases · 2022Review
- The Molecular Basis and Therapeutic Potential of Leukemia Inhibitory Factor in Cancer Cachexia.Cancers · 2022Review
- Leukemia inhibitory factor drives glucose metabolic reprogramming to promote breast tumorigenesis.Cell death & disease · 2022Article
- Leukemia Inhibitory Factor: An Important Cytokine in Pathologies and Cancer.Biomolecules · 2022Review
- Cancer-associated adipocytes promote the invasion and metastasis in breast cancer through LIF/CXCLs positive feedback loop.International journal of biological sciences · 2022Article
- LIFR inhibition enhances the therapeutic efficacy of HDAC inhibitors in triple negative breast cancer.Communications biology · 2021Article
- Article
- Leukemia inhibitory factor is involved in the pathogenesis of NSCLC through activation of the STAT3 signaling pathway.Oncology letters · 2021Article
- Cellular senescence or stemness: hypoxia flips the coin.Journal of experimental & clinical cancer research : CR · 2021Review
- Emerging Perspectives on Leukemia Inhibitory Factor and its Receptor in Cancer.Frontiers in oncology · 2021Review
- Hypoxia-induced downregulation of B-cell translocation gene 3 confers resistance to radiation therapy of colorectal cancer.Journal of cancer research and clinical oncology · 2020Article
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 2 countries.
Funding
Abstract
Leukemia inhibitory factor (LIF), a multi-functional cytokine, has a complex role in cancer. While LIF induces the differentiation of several myeloid leukemia cells and inhibits their growth, it also promotes tumor progression, metastasis and chemoresistance in many solid tumors. LIF is frequently overexpressed in a variety of human tumors and its overexpression is often associated with poor prognosis of patients. Currently, the mechanism for LIF overexpression in tumor cells is not well-understood. Here, we report that hypoxia, a hallmark of solid tumors, induced LIF mRNA expression in human colorectal cancer cells. Analysis of LIF promoter revealed several hypoxia-responsive elements (HREs) that can specifically interact with and be transactivated by HIF-2α but not HIF-1α. Consistently, ectopic expression of HIF-2α but not HIF-1α transcriptionally induced LIF expression levels in cells. Knockdown of endogenous HIF-2α but not HIF-1α by siRNA largely abolished the induction of LIF by hypoxia in cells. Furthermore, there is a strong association of HIF-2α overexpression with LIF overexpression in human colorectal cancer specimens. In summary, results from this study demonstrate that hypoxia induces LIF expression in human cancer cells mainly through HIF-2α, which could be an important underlying mechanism for LIF overexpression in human cancers.
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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.