ArticlePloS one2015
HIF-1α Promotes Epithelial-Mesenchymal Transition and Metastasis through Direct Regulation of ZEB1 in Colorectal Cancer.
Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 198 papers.
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Who cites it
198 citing papers in PubMed, 257 citations in OpenAlex.
- Overexpression of annexin A4 indicates poor prognosis and promotes tumor metastasis of hepatocellular carcinoma.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2016Trial
- Mechanisms Underlying the Coordination of EMT and Glycolysis Mediated by Hypoxia and Glucose.Current issues in molecular biology · 2026Article
- Evaluation of Serum HIF-1α as a Hypoxia-Related Biomarker in Patients with Malignant Salivary Gland Neoplasms.Biomedicines · 2026Article
- Cholesterol-Lowering Treatment Blocks Epithelial-Mesenchymal Transition (EMT) Associated Invasiveness and Drug Resistance in Breast and Colorectal Adenocarcinoma Models.Cancer medicine · 2026Article
- Tumor-enriched circRNA TAFCR1 drives cancer progression and metastasis by disrupting UBE1-dependent TRIM21-mediated CD44 ubiquitination.Biomarker research · 2026Article
- Cancer-associated adipomes promote invadopodia formation and enhance metastatic potential in triple-negative breast cancer.NPJ breast cancer · 2026Article
- Preoperative low-attenuation area on computed tomography is associated with recurrence after curative resection for non-small-cell lung cancer.Cancer imaging : the official publication of the International Cancer Imaging Society · 2026Article
- Oncogenic cell fate decision in breast epithelial cells I: growth factors and mechanisms.Research square · 2026Article
- The Pro-Metastatic Roles of ROS.Antioxidants (Basel, Switzerland) · 2026Review
- Spatial heterogeneity of malignant molecular markers in glioma revealed by stereotactic biopsy.Discover oncology · 2026Article
- Implication of Epigenetic Alterations of ZEB1 in Colorectal Cancer (CRC) Pathogenesis and Therapy Development.Current issues in molecular biology · 2026Review
- Identification, functional insights and therapeutic targeting of EMT tumour states.Nature reviews. Cancer · 2026Review
- Lactate, a Spearhead of Cancer Aggressiveness: Metabolic Reprogramming, Immune Suppression, and Metastatic Progression.Medical principles and practice : international journal of the Kuwait University, Health Science Centre · 2026Review
- Circulating tumour cells and circulating tumour DNA in head and neck cancer: from molecular insights to clinical impact.Cancer metastasis reviews · 2025Review
- E-Cadherin Regulates HIF1-α In Vitro in Induced 3D Spheroid Models of Human Breast Cancer Through Both mTOR and Notch1 Signaling.Biomedicines · 2025Article
- Clinical and Genomic Features and Prognostic Biomarkers of Oligometastatic Nonsmall Cell Lung Cancer.Clinical lung cancer · 2025Article
- Oncostatin M orchestrates collective epithelial migration via HIF1A activation.bioRxiv : the preprint server for biology · 2025Article
- LncRNAs in hypoxic microenvironment; insight in their impact in cancer biology.Functional & integrative genomics · 2025Review
- Hypoxia-inducible factor-1α at the invasive tumor front in oral squamous cell carcinoma.World journal of experimental medicine · 2025Article
- Deciphering Radiotherapy Resistance: A Proteomic Perspective.Proteomes · 2025Review
138 more citing papers are in PubMed but not listed here.
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
It is well recognized that hypoxia-inducible factor 1 alpha (HIF-1α) is involved in cancer metastasis, chemotherapy and poor prognosis. We previously found that deferoxamine, a hypoxia-mimetic agent, induces epithelial-mesenchymal transition (EMT) in colorectal cancer. Therefore, here we explored a new molecular mechanism for HIF-1α contributing to EMT and cancer metastasis through binding to ZEB1. In this study, we showed that overexpression of HIF-1α with adenovirus infection promoted EMT, cell invasion and migration in vitro and in vivo. On a molecular level, HIF-1α directly binding to the proximal promoter of ZEB1 via hypoxia response element (HRE) sites thus increasing the transactivity and expression of ZEB1. In addition, inhibition of ZEB1 was able to abrogate the HIF-1α-induced EMT and cell invasion. HIF-1α expression was highly correlated with the expression of ZEB1 in normal colorectal epithelium, primary and metastatic CRC tissues. Interestingly, both HIF-1α and ZEB1 were positively associated with Vimentin, an important mesenchymal marker of EMT, whereas negatively associated with E-cadherin expression. These findings suggest that HIF-1α enhances EMT and cancer metastasis by binding to ZEB1 promoter in CRC. HIF-1α and ZEB1 are both widely considered as tumor-initiating factors, but our results demonstrate that ZEB1 is a direct downstream of HIF-1α, suggesting a novel molecular mechanism for HIF-1α-inducing EMT and cancer metastasis.
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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.