ArticleOncogene2014
Hypoxia-driven osteopontin contributes to breast tumor growth through modulation of HIF1α-mediated VEGF-dependent angiogenesis.
Article in Oncogene, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 73 papers.
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Who cites it
73 citing papers in PubMed, 128 citations in OpenAlex.
- The HIF-Mediated PI3K-AKT Signaling Pathway Is a Key Signaling Pathway Triggering Testicular Spermatogenic Disorders in Yaks with Cryptorchidism.Veterinary sciences · 2026Article
- Intracellular Osteopontin of Macrophages Promotes Carotid Plaques Formation by Inducing Foam Cells and Releasing Proinflammatory Cytokines.Journal of the American Heart Association · 2026Article
- Research progress on the correlation between OPN and immune escape of gastric cancer.Clinical and experimental medicine · 2026Review
- SPP1 promotes the metastasis of liver cancer cells through modulation of the MT1L/vimentin axis.American journal of cancer research · 2026Article
- Exercise-responsive microRNA networks and extracellular vesicle-mediated microRNA signaling in breast cancer: linking tumor signaling, systemic crosstalk, and clinical relevance.Frontiers in oncology · 2026Review
- Microglia-vascular interactions after spinal cord injury: regulatory mechanisms and therapeutic advances.Frontiers in immunology · 2026Review
- ICOSL: more than a trigger of ICOS function.Cell communication and signaling : CCS · 2025Review
- Role of Matricellular Proteins in Endothelial Cell Inflammation and Atherosclerosis.Antioxidants (Basel, Switzerland) · 2025Review
- Deciphering hypoxia's role in hepatocellular carcinoma prognosis with single-cell approaches.Discover oncology · 2025Article
- Epithelial-to-mesenchymal transition (EMT) and cancer metastasis: the status quo of methods and experimental models 2025.Molecular cancer · 2025Review
- Review
- Integrin signaling in tumor biology: mechanisms of intercellular crosstalk and emerging targeted therapies.PeerJ · 2025Review
- Osteopontin: A Key Multifaceted Regulator in Tumor Progression and Immunomodulation.Biomedicines · 2024Review
- Review
- Osteopontin secreted from obese adipocytes enhances angiogenesis and promotes progression of pancreatic ductal adenocarcinoma in obesity.Cellular oncology (Dordrecht, Netherlands) · 2024Article
- Role of exosomes in modulating non-small cell lung cancer radiosensitivity.Frontiers in pharmacology · 2024Review
- Exploring the multifaceted role of obesity in breast cancer progression.Frontiers in cell and developmental biology · 2024Review
- Role of osteopontin in cancer development and treatment.Heliyon · 2023Review
- Thrombotic Alterations under Perinatal Hypoxic Conditions: HIF and Other Hypoxic Markers.International journal of molecular sciences · 2023Review
- The Intracellular and Secreted Sides of Osteopontin and Their Putative Physiopathological Roles.International journal of molecular sciences · 2023Review
13 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Hypoxia is a salient feature of most solid tumors, and hypoxic adaptation of cancer cells has crucial implications in propagation of malignant clonal cell population. Osteopontin (OPN) has been identified as a hypoxia-responsive gene, but the mechanistic and regulatory role of OPN under hypoxia is less characterized. The present study identifies the existence of a positive inter-regulatory loop between hypoxia and OPN. We have shown that hypoxia induces OPN expression in breast cancer cells; however, the expression was found to be HIF1α independent. OPN enabled transcriptional upregulation of HIF1α expression both under normoxia and hypoxia, whereas stability of HIF1α protein in breast cancer cells remained unaffected. Moreover, we have shown that OPN induces integrin-linked kinase (ILK)/Akt-mediated nuclear factor (NF)-κB p65 activation leading to HIF1α-dependent vascular endothelial growth factor (VEGF) expression and angiogenesis in response to hypoxia. These in vitro data are biologically important as OPN expressing cells induce greater tumor growth and angiogenesis through enhanced expressions of proangiogenic molecules as compared with control. Immunohistochemical analysis of human breast cancer specimens revealed significant correlation between OPN and HIF1α but not HIF2α. Elevated expression of HIF1α and OPN was observed in pre-neoplastic and early stage infiltrating ductal carcinoma implicating the role of these proteins in neoplastic progression of breast cancer. Together, our results substantiate the prime role of OPN in cellular adaptation through ILK and NF-κB-mediated HIF1α-dependent VEGF expression in response to hypoxia that ultimately controls breast cancer progression and angiogenesis. Our study reinforces the fact that targeting OPN and its regulated signaling network hold important therapeutic implications.
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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.