ArticleOncogene2020
Context-dependent activation of SIRT3 is necessary for anchorage-independent survival and metastasis of ovarian cancer cells.
Article in Oncogene, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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Who cites it
41 citing papers in PubMed, 62 citations in OpenAlex.
- Generation and Characterization of Adaptive Anoikis-Resistant Cells Using Cyclic Attachment-Detachment Culture of Cancer Cells.Bio-protocol · 2026Article
- RHOV Is a Detachment-Responsive Rho GTPase Necessary for Ovarian Cancer Peritoneal Metastasis.Cancer research · 2026Article
- Synthetic Novel Flavonoids SZQ-4 Suppress Osteoclastogenesis and Ameliorate Osteoporosis via Inhibiting Reactive Oxygen Species and Regulating SIRT3.Antioxidants (Basel, Switzerland) · 2026Article
- Mitochondrial Long Non-Coding RNAs in Gynecological Cancers: Pathogenic Signaling Pathways and Therapeutic Opportunities.Current issues in molecular biology · 2026Review
- Anoikis resistance and metastasis of ovarian cancer can be overcome by CDK8/19 mediator kinase inhibition.JCI insight · 2026Article
- An optimized protocol for metabolic measurement in 3D tumor spheroids derived from primary and established glioblastoma cells.PloS one · 2026Article
- Emerging Role of Sirtuins-Mediated Ferroptosis in Hepatocellular Carcinoma Progression: Mechanisms and Therapeutic Perspectives.Journal of hepatocellular carcinoma · 2026Review
- Mapping transcriptomic signatures downstream of mitochondrial superoxide dismutase SOD2 in OVCA433 multicellular aggregates.Advances in redox research · 2025Article
- Anoikis resistance and cancer.BMC cancer · 2025Review
- CAMKKβ supports growth and viability of epithelial ovarian cancer in vitro and in vivo.Scientific reports · 2025Article
- Gα13 Promotes Clonogenic Growth by Increasing Tolerance to Oxidative Metabolic Stress in Prostate Cancer Cells.International journal of molecular sciences · 2025Article
- SIRT3 Functions as an Eraser of Histone H3K9 Lactylation to Modulate Transcription for Inhibiting the Progression of Esophageal Cancer.Molecular & cellular proteomics : MCP · 2025Article
- Article
- Inhibition of SIRT3 by a specific inhibitor induces cellular senescence and growth arrest of ovarian granulosa cell tumor via p53 and NF-κB axis.Frontiers in pharmacology · 2025Article
- Sirtuin insights: bridging the gap between cellular processes and therapeutic applications.Naunyn-Schmiedeberg's archives of pharmacology · 2024Review
- GPX3 supports ovarian cancer tumor progression in vivo and promotes expression of GDF15.Gynecologic oncology · 2024Article
- The Role of Selenium and Manganese in the Formation, Diagnosis and Treatment of Cervical, Endometrial and Ovarian Cancer.International journal of molecular sciences · 2023Review
- Glutathione peroxidase 2 knockdown suppresses gastric cancer progression and metastasis via regulation of kynurenine metabolism.Oncogene · 2023Article
- Mitochondrial Dysfunction: A Cellular and Molecular Hub in Pathology of Metabolic Diseases and Infection.Journal of clinical medicine · 2023Review
- Metabolic reprogramming of the ovarian cancer microenvironment in the development of antiangiogenic resistance.Acta biochimica et biophysica Sinica · 2023Review
Corrections and comments
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Authors and funding
16 authors at 4 institutions in 2 countries.
Funding
Abstract
Tumor cells must alter their antioxidant capacity for maximal metastatic potential. Yet the antioxidant adaptations required for ovarian cancer transcoelomic metastasis, which is the passive dissemination of cells in the peritoneal cavity, remain largely unexplored. Somewhat contradicting the need for oxidant scavenging are previous observations that expression of SIRT3, a nutrient stress sensor and regulator of mitochondrial antioxidant defenses, is often suppressed in many primary tumors. We have discovered that this mitochondrial deacetylase is specifically upregulated in a context-dependent manner in cancer cells. SIRT3 activity and expression transiently increased following ovarian cancer cell detachment and in tumor cells derived from malignant ascites of high-grade serous adenocarcinoma patients. Mechanistically, SIRT3 prevents mitochondrial superoxide surges in detached cells by regulating the manganese superoxide dismutase (SOD2). This mitochondrial stress response is under dual regulation by SIRT3. SIRT3 rapidly increases SOD2 activity as an early adaptation to cellular detachment, which is followed by SIRT3-dependent increases in SOD2 mRNA during sustained anchorage-independence. In addition, SIRT3 inhibits glycolytic capacity in anchorage-independent cells thereby contributing to metabolic changes in response to detachment. While manipulation of SIRT3 expression has few deleterious effects on cancer cells in attached conditions, SIRT3 upregulation and SIRT3-mediated oxidant scavenging are required for anoikis resistance in vitro following matrix detachment, and both SIRT3 and SOD2 are necessary for colonization of the peritoneal cavity in vivo. Our results highlight the novel context-specific, pro-metastatic role of SIRT3 in ovarian cancer.
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