ArticleCell death & disease2013
Manganese superoxide dismutase promotes anoikis resistance and tumor metastasis.
Article in Cell death & disease, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 72 papers.
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Who cites it
72 citing papers in PubMed, 152 citations in OpenAlex.
- Manganese Superoxide Dismutase: Structure, Function, and Implications in Human Disease.Antioxidants (Basel, Switzerland) · 2025Review
- Cancer metastasis: molecular mechanisms and therapeutic interventions.Molecular biomedicine · 2025Review
- Upregulated FSP1 by GPD1/1L mediated lipid droplet accumulation enhances ferroptosis resistance and peritoneal metastasis in gastric cancer.Cell communication and signaling : CCS · 2025Article
- 6-Gingerol Induced Apoptosis and Cell Cycle Arrest in Glioma Cells via MnSOD and ERK Phosphorylation Modulation.Biomolecules & therapeutics · 2025Article
- GRP94 promotes anoikis resistance and peritoneal metastasis through YAP/TEAD1 pathway in gastric cancer.iScience · 2024Article
- Dose-Dependent Effect of Mitochondrial Superoxide Dismutase Gene Overexpression on Radioresistance of HEK293T Cells.International journal of molecular sciences · 2023Article
- Anoikis resistance and immune escape mediated by Epstein-Barr virus-encoded latent membrane protein 1-induced stabilization of PGC-1α promotes invasion and metastasis of nasopharyngeal carcinoma.Journal of experimental & clinical cancer research : CR · 2023Article
- Anoikis resistance--protagonists of breast cancer cells survive and metastasize after ECM detachment.Cell communication and signaling : CCS · 2023Review
- IGFBP1 Sustains Cell Survival during Spatially-Confined Migration and Promotes Tumor Metastasis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Article
- Expression Changes of SIRT1 and FOXO3a Significantly Correlate with Oxidative Stress Resistance Genes in AML Patients.Indian journal of hematology & blood transfusion : an official journal of Indian Society of Hematology and Blood Transfusion · 2023Article
- Succinyl-CoA ligase ADP-forming subunit beta promotes stress granule assembly to regulate redox and drive cancer metastasis.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- The Metabolic Landscape of Breast Cancer and Its Therapeutic Implications.Molecular diagnosis & therapy · 2023Review
- Molecular profiles of single circulating tumor cells from early breast cancer patients with different lymph node statuses.Thoracic cancer · 2023Article
- GPX3 expression was down-regulated but positively correlated with poor outcome in human cancers.Frontiers in oncology · 2023Article
- Effects of Antioxidant Gene Overexpression on Stress Resistance and Malignization In Vitro and In Vivo: A Review.Antioxidants (Basel, Switzerland) · 2022Review
- A Bioinformatics-Based Analysis of an Anoikis-Related Gene Signature Predicts the Prognosis of Patients with Low-Grade Gliomas.Brain sciences · 2022Article
- HuR-dependent SOD2 protein synthesis is an early adaptation to anchorage-independence.Redox biology · 2022Article
- Review
- Anoikis resistance in diffuse glioma: The potential therapeutic targets in the future.Frontiers in oncology · 2022Review
- Targeting Oxidative Phosphorylation-Proteasome Activity in Extracellular Detached Cells Promotes Anoikis and Inhibits Metastasis.Life (Basel, Switzerland) · 2021Article
12 more citing papers are in PubMed but not listed here.
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Authors and funding
12 authors at 6 institutions in 2 countries.
Funding
Abstract
Normal cells require adhesion to extracellular matrix for survival. Cell detachment causes a drastic increase in reactive oxygen species (ROS) that promotes anoikis. In the present study, we observed that upon detachment from matrix, human mammary epithelial cells strongly upregulate manganese superoxide dismutase (MnSOD, or SOD2), a principal mitochondrial antioxidant enzyme that detoxifies ROS through dismutation of superoxide. Induction of MnSOD by cell detachment is dependent on the NFκB transcription factor. Detachment of mammary epithelial cells potently increases mitochondrial superoxide levels, which are further elevated by depletion of MnSOD in suspended cells. Consequently, cells depleted of MnSOD are hypersensitive to matrix detachment and exhibit increased anoikis. These results suggest that detachment-induced MnSOD counters mitochondrial superoxide accumulation and confers anoikis resistance. Taken together with our previous finding that detached cells evade excessive ROS production by attenuating oxidative metabolism of glucose, we conclude that mammary epithelial cells coordinate their responses to detachment through increasing MnSOD and decreasing ROS generation from mitochondrial glucose oxidation, thereby mitigating anoikis. Anoikis is a barrier to tumor metastasis. Indeed, MnSOD expression is elevated in human breast cancer metastases compared with primary tumors. Expression of MnSOD correlates with histologic tumor grades in human cancer and contributes to cancer cell's resistance to anoikis. Our study suggests that inhibition of ROS detoxification coupled with stimulation of glucose oxidative metabolism may be an efficient strategy to enhance anoikis and block metastasis.
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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.