ArticlePloS one2014
Down regulation of Wnt signaling mitigates hypoxia-induced chemoresistance in human osteosarcoma cells.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 41 citations in OpenAlex.
- Linking Environmental Hazards to Osteosarcoma Development: A Comprehensive Review.Cancer management and research · 2025Review
- Wnt/β-catenin signaling pathway: an attractive potential therapeutic target in osteosarcoma.Frontiers in oncology · 2024Review
- Exosomes in Bone Cancer: Unveiling their Vital Role in Diagnosis, Prognosis, and Therapeutic Advancements.Journal of Cancer · 2024Review
- P53‑microRNA interactions regulate the response of colorectal tumor cells to oxaliplatin under normoxic and hypoxic conditions.Oncology reports · 2023Article
- Mitochondrial leak metabolism induces the Spemann-Mangold Organizer via Hif-1α in Xenopus.Developmental cell · 2023Article
- Chemoresistance-Related Stem Cell Signaling in Osteosarcoma and Its Plausible Contribution to Poor Therapeutic Response: A Discussion That Still Matters.International journal of molecular sciences · 2022Review
- Plateau Adaptation Gene Analyses Reveal Transcriptomic, Proteomic, and Dual Omics Expression in the Lung Tissues of Tibetan and Yorkshire Pigs.Animals : an open access journal from MDPI · 2022Article
- Effects of microenvironment in osteosarcoma on chemoresistance and the promise of immunotherapy as an osteosarcoma therapeutic modality.Frontiers in immunology · 2022Review
- Cancer Stem Cells as a Source of Drug Resistance in Bone Sarcomas.Journal of clinical medicine · 2021Review
- High expression of ABCG2 is associated with chemotherapy resistance of osteosarcoma.Journal of orthopaedic surgery and research · 2021Article
- Recent Insights into Therapy Resistance in Osteosarcoma.Cancers · 2020Review
- Sarcoma treatment in the era of molecular medicine.EMBO molecular medicine · 2020Review
- Review
- Article
- New Insights about the Wnt/β-Catenin Signaling Pathway in Primary Bone Tumors and Their Microenvironment: A Promising Target to Develop Therapeutic Strategies?International journal of molecular sciences · 2019Review
- microRNA-758 inhibits the malignant phenotype of osteosarcoma cells by directly targetingAmerican journal of cancer research · 2019Article
- Expression of circ_001569 is upregulated in osteosarcoma and promotes cell proliferation and cisplatin resistance by activating the Wnt/β-catenin signaling pathway.Oncology letters · 2018Article
- Inhibition of WNT/β-catenin signaling under serum starvation and hypoxia induces adipocytic transdifferentiation in human leiomyoma cells.Laboratory investigation; a journal of technical methods and pathology · 2018Article
- Wnt Signaling in Ewing Sarcoma, Osteosarcoma, and Malignant Peripheral Nerve Sheath Tumors.Current osteoporosis reports · 2017Review
- Bone microenvironment signals in osteosarcoma development.Cellular and molecular life sciences : CMLS · 2015Review
Corrections and comments
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Authors and funding
6 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Osteosarcoma (OS) is the most common type of solid bone cancer and remains the second leading cause of cancer-related death for children and young adults. Hypoxia is an element intrinsic to most solid-tumor microenvironments, including that of OS, and is associated with resistance to therapy, poor survival, and a malignant phenotype. Cells respond to hypoxia through alterations in gene expression, mediated most notably through the hypoxia-inducible factor (HIF) class of transcription factors. Here we investigate hypoxia-induced changes in the Wnt/β-catenin signaling pathway, a key signaling cascade involved in OS pathogenesis. We show that hypoxia results in increased expression and signaling activation of HIF proteins in human osteosarcoma cells. Wnt/β-catenin signaling is down-regulated by hypoxia in human OS cells, as demonstrated by decreased active β-catenin protein levels and axin2 mRNA expression (p<0.05). This down-regulation appears to rely on both HIF-independent and HIF-dependent mechanisms, with HIF-1α standing out as an important regulator. Finally, we show that hypoxia results in resistance of human OS cells to doxorubicin-mediated toxicity (6-13 fold increase, p<0.01). These hypoxic OS cells can be sensitized to doxorubicin treatment by further inhibition of the Wnt/β-catenin signaling pathway (p<0.05). These data support the conclusion that Wnt/β-catenin signaling is down-regulated in human OS cells under hypoxia and that this signaling alteration may represent a viable target to combat chemoresistant OS subpopulations in a hypoxic niche.
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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.