ArticleMolecular cancer2014
Oncogenic transformation of mesenchymal stem cells decreases Nrf2 expression favoring in vivo tumor growth and poorer survival.
Article in Molecular cancer, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers, 1 of them a synthesis that pooled it.
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Who cites it
21 citing papers in PubMed, 1 synthesis or guideline pooled it, 40 citations in OpenAlex.
- The dual role of Nrf2 in melanoma: a systematic review.BMC molecular and cell biology · 2023Pooled it
- GPX1 expression promotes stemness and aggressiveness in myxoid liposarcomas.International journal of biological sciences · 2025Article
- Targeting Nrf2 and NF-κB Signaling Pathways in Cancer Prevention: The Role of Apple Phytochemicals.Molecules (Basel, Switzerland) · 2023Review
- Review
- A new frontier in temporomandibular joint osteoarthritis treatment: Exosome-based therapeutic strategy.Frontiers in bioengineering and biotechnology · 2022Review
- NRF2: A crucial regulator for mitochondrial metabolic shift and prostate cancer progression.Frontiers in physiology · 2022Review
- A Novel Six-Gene Signature for Prognosis Prediction in Ovarian Cancer.Frontiers in genetics · 2020Article
- Unscheduled HDAC4 repressive activity in human fibroblasts triggers TP53-dependent senescence and favors cell transformation.Molecular oncology · 2018Article
- Redox Signaling by Reactive Electrophiles and Oxidants.Chemical reviews · 2018Review
- Metformin Promotes HaCaT Cell Apoptosis through Generation of Reactive Oxygen Species via Raf-1-ERK1/2-Nrf2 Inactivation.Inflammation · 2018Article
- Propoxur enhances MMP-2 expression and the corresponding invasion of human breast cancer cells via the ERK/Nrf2 signaling pathway.Oncotarget · 2017Article
- Reduced mRNA expression levels of NFE2L2 are associated with poor outcome in breast cancer patients.BMC cancer · 2016Article
- Lysosomal acid lipase in mesenchymal stem cell stimulation of tumor growth and metastasis.Oncotarget · 2016Article
- Epigenetic modifications of triterpenoid ursolic acid in activating Nrf2 and blocking cellular transformation of mouse epidermal cells.The Journal of nutritional biochemistry · 2016Article
- A Case-Control Study of Involvement of Oxidative DNA Damage and Alteration of Antioxidant Defense System in Patients with Basal Cell Carcinoma: Modulation by Tumor Removal.Oxidative medicine and cellular longevity · 2016Article
- Mesenchymal stem cell in vitro labeling by hybrid fluorescent magnetic polymeric particles for application in cell tracking.Medical molecular morphology · 2015Article
- The redox biology network in cancer pathophysiology and therapeutics.Redox biology · 2015Review
- Gene expression profiling of ovarian carcinomas and prognostic analysis of outcome.Journal of ovarian research · 2015Article
- Raf/ERK/Nrf2 signaling pathway and MMP-7 expression involvement in the trigonelline-mediated inhibition of hepatocarcinoma cell migration.Food & nutrition research · 2015Article
- Cytoprotection "gone astray": Nrf2 and its role in cancer.OncoTargets and therapy · 2014Review
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
Abstract
backgroundThe transcription factor Nrf2 is a key regulator of the cellular antioxidant response, and its activation by chemoprotective agents has been proposed as a potential strategy to prevent cancer. However, activating mutations in the Nrf2 pathway have been found to promote tumorigenesis in certain models. Therefore, the role of Nrf2 in cancer remains contentious.
methodsWe employed a well-characterized model of stepwise human mesenchymal stem cell (MSC) transformation and breast cancer cell lines to investigate oxidative stress and the role of Nrf2 during tumorigenesis. The Nrf2 pathway was studied by microarray analyses, qRT-PCR, and western-blotting. To assess the contribution of Nrf2 to transformation, we established tumor xenografts with transformed MSC expressing Nrf2 (n = 6 mice per group). Expression and survival data for Nrf2 in different cancers were obtained from GEO and TCGA databases. All statistical tests were two-sided.
resultsWe found an accumulation of reactive oxygen species during MSC transformation that correlated with the transcriptional down-regulation of antioxidants and Nrf2-downstream genes. Nrf2 was repressed in transformed MSC and in breast cancer cells via oncogene-induced activation of the RAS/RAF/ERK pathway. Furthermore, restoration of Nrf2 function in transformed cells decreased reactive oxygen species and impaired in vivo tumor growth (P = 0.001) by mechanisms that included sensitization to apoptosis, and a decreased hypoxic/angiogenic response through HIF-1α destabilization and VEGFA repression. Microarray analyses showed down-regulation of Nrf2 in a panel of human tumors and, strikingly, low Nrf2 expression correlated with poorer survival in patients with melanoma (P = 0.0341), kidney (P = 0.0203) and prostate (P = 0.00279) cancers.
conclusionsOur data indicate that oncogene-induced Nrf2 repression is an adaptive response for certain cancers to acquire a pro-oxidant state that favors cell survival and in vivo tumor growth.
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