ArticleChinese journal of cancer research = Chung-kuo yen cheng yen chiu2021
Mitochondrial malic enzyme 2 promotes breast cancer metastasis via stabilizing HIF-1α under hypoxia.
Article in Chinese journal of cancer research = Chung-kuo yen cheng yen chiu, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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14 citing papers in PubMed, 15 citations in OpenAlex.
- Intracellular lactic acidosis reprograms glycolysis and mitochondrial anaplerosis in cancer cells.The Journal of biological chemistry · 2026Article
- Small interfering RNA (siRNA)-based targeting breast cancer therapy.Discover oncology · 2026Review
- Malic enzyme 2 suppresses PINK1-Parkin-mediated mitophagy by stabilizing ATAD3A via competitive interaction with TRIM25.Cell death & disease · 2026Article
- NADPH-Related Enzymes and Cancer: Facts and Insights Into the Application of Immunohistochemistry.Biochemistry research international · 2026Review
- The Interdependence of Carbon Substrates and Metabolic Pathways Enables the Metabolic Plasticity of Cancer Cells.Advances in experimental medicine and biology · 2026Review
- PRMT1-mediated methylation of ME2 promotes hepatocellular carcinoma growth by inhibiting ubiquitination.Cell death & disease · 2024Article
- Malic enzymes in cancer: Regulatory mechanisms, functions, and therapeutic implications.Redox biology · 2024Review
- Therapeutic mechanisms of modified Jiawei Juanbi decoction in early knee osteoarthritis: A multimodal analysis.Heliyon · 2024Article
- Mitochondrial inhibitors: a new horizon in breast cancer therapy.Frontiers in pharmacology · 2024Review
- Suppression of the human malic enzyme 2 modifies energy metabolism and inhibits cellular respiration.Communications biology · 2023Article
- siRNA and targeted delivery systems in breast cancer therapy.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2023Review
- Targeting Mitochondria with ClpP Agonists as a Novel Therapeutic Opportunity in Breast Cancer.Cancers · 2023Review
- Mitochondrial Matrix Protease ClpP Agonists Inhibit Cancer Stem Cell Function in Breast Cancer Cells by Disrupting Mitochondrial Homeostasis.Cancer research communications · 2022Article
- The Role of Hypoxia-Inducible Factor Isoforms in Breast Cancer and Perspectives on Their Inhibition in Therapy.Cancers · 2022Review
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectiveα-ketoglutarate (α-KG) is the substrate to hydroxylate collagen and hypoxia-inducible factor-1α (HIF-1α), which are important for cancer metastasis. Previous studies have shown that the upregulation of collagen prolyl 4-hydroxylase in breast cancer cells stabilizes the expression of HIF-1α by depleting α-KG levels. We hypothesized that mitochondrial malic enzyme 2 (ME2) might also affect HIF-1α expression via modulating α-KG levels in breast cancer cells.
methodsWe evaluated ME2 protein expression in 100 breast cancer patients using immunohistochemistry and correlated with clinicopathological indicators. The effect of ME2 knockout on cancer metastasis was evaluated using an orthotopic breast cancer model. The effect of ME2 knockout or knockdown on the levels of α-KG and HIF-1α proteins in breast cancer cell lines was determined both
resultsME2 was found to be upregulated in the human breast cancerous tissues compared with the matched precancerous tissues (P<0.001). The elevated expression of ME2 was associated with a poor prognosis (P=0.019). ME2 upregulation was also related to lymph node metastasis (P=0.016), pathological staging (P=0.033), and vascular cancer embolus (P=0.014). Also, ME2 knockout significantly inhibited lung metastasis
conclusionsOur results provide evidence that upregulation of ME2 is associated with a poor prognosis of breast cancer patients and propose a mechanistic understanding of a link between ME2 and breast cancer metastasis.
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