ArticleOncotarget2015
HIF isoforms have divergent effects on invasion, metastasis, metabolism and formation of lipid droplets.
Article in Oncotarget, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed.
- Glucose stimulated CEST MRI pHe mapping for improved differentiation of tumors with altered hypoxia inducible factor 1alpha expression.Scientific reports · 2025Article
- Tet Transgene Activation is Disrupted in Lipogenic Triple Negative Breast Cancer Cells.ACS synthetic biology · 2025Article
- Hypoxia-inducible factors: master regulators of hypoxic tumor immune escape.Journal of hematology & oncology · 2022Review
- HIF and COX-2 expression in triple negative breast cancer cells with hypoxia and 5-fluorouracil.Current cancer reports · 2020Article
- Lipid droplets: platforms with multiple functions in cancer hallmarks.Cell death & disease · 2020Review
- MRI and MRS of intact perfused cancer cell metabolism, invasion, and stromal cell interactions.NMR in biomedicine · 2019Review
- Molecular and functional imaging insights into the role of hypoxia in cancer aggression.Cancer metastasis reviews · 2019Review
- Hypoxia Induced ER Stress Response as an Adaptive Mechanism in Cancer.International journal of molecular sciences · 2019Review
- Key indexes and the emerging tool for tumor microenvironment editing.American journal of cancer research · 2019Review
- Transcatheter arterial embolization combined with hypoxia-replicative oncolytic adenovirus perfusion enhances the therapeutic effect of hepatic carcinoma.Cancer management and research · 2019Article
- Microfluidics in Malignant Glioma Research and Precision Medicine.Advanced biosystems · 2018Article
- Metabolic consequences of HIF silencing in a triple negative human breast cancer xenograft.Oncotarget · 2018Article
- Hypoxia Inducible Factors Modify Collagen I Fibers in MDA-MB-231 Triple Negative Breast Cancer Xenografts.Neoplasia (New York, N.Y.) · 2018Article
- Prognostic Role of Hypoxia-Inducible Factor-2α Tumor Cell Expression in Cancer Patients: A Meta-Analysis.Frontiers in oncology · 2018Article
- Similarity in the functions of HIF-1α and HIF-2α proteins in cervical cancer cells.Oncology letters · 2017Article
- Lipid Droplets: A Key Cellular Organelle Associated with Cancer Cell Survival under Normoxia and Hypoxia.International journal of molecular sciences · 2016Review
- Hypoxia and metabolic adaptation of cancer cells.Oncogenesis · 2016Review
Corrections and comments
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Authors and funding
8 authors.
Funding
Abstract
Cancer cells adapt to hypoxia by the stabilization of hypoxia inducible factor (HIF)-α isoforms that increase the transcription of several genes. Among the genes regulated by HIF are enzymes that play a role in invasion, metastasis and metabolism. We engineered triple (estrogen receptor/progesterone receptor/HER2/neu) negative, invasive MDA-MB-231 and SUM149 human breast cancer cells to silence the expression of HIF-1α, HIF-2α or both isoforms of HIF-α. We determined the metabolic consequences of HIF silencing and the ability of HIF-α silenced cells to invade and degrade the extracellular matrix (ECM) under carefully controlled normoxic and hypoxic conditions. We found that silencing HIF-1α alone was not sufficient to attenuate invasiveness in both MDA-MB-231 and SUM149 cell lines. Significantly reduced metastatic burden was observed in single (HIF-1α or HIF-2α) and double α-isoform silenced cells, with the reduction most evident when both HIF-1α and HIF-2α were silenced in MDA-MB-231 cells. HIF-2α played a major role in altering cell metabolism. Lipids and lipid droplets were significantly reduced in HIF-2α and double silenced MDA-MB-231 and SUM149 cells, implicating HIF in their regulation. In addition, lactate production and glucose consumption were reduced. These results suggest that in vivo, cells in or near hypoxic regions are likely to be more invasive. The data indicate that targeting HIF-1α alone is not sufficient to attenuate invasiveness, and that both HIF-1α and HIF-2α play a role in the metastatic cascade in these two cell lines.
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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.