ArticleOncogene2017
Phosphorylation-mediated activation of LDHA promotes cancer cell invasion and tumour metastasis.
Article in Oncogene, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 182 papers.
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Who cites it
182 citing papers in PubMed, 304 citations in OpenAlex.
- PRAS40 enhances glycolysis by facilitating G6PI/PGK1/LDHA complex assembly in colorectal cancer.Discover oncology · 2026Article
- Article
- NIPAL1 Drives a Metabolic-Epigenetic Feedback Loop to Promote Lactate-Mediated Immune Evasion in Esophageal Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- [Research progress on protein lactylation modification in malignant tumors].Beijing da xue xue bao. Yi xue ban = Journal of Peking University. Health sciences · 2026Review
- Mechanism of FoxO1 in the Metabolic Shift of Fetal Rat Heart.Molecules (Basel, Switzerland) · 2026Article
- Suppression of Tumor Aggression Through Metabolic Reprogramming via Oxamate Targeting LDHA.International journal of molecular sciences · 2026Review
- Review
- Metabolic Vulnerabilities as a Therapeutic Target in Breast Cancer.Current oncology (Toronto, Ont.) · 2026Review
- AFP confers the resistance of lenvatinib in hepatocellular carcinoma by activating PI3K/AKT/LDHA signaling axis.Discover oncology · 2026Article
- The moonlighting functions of glycolytic enzymes in tumorigenesis.Cellular oncology (Dordrecht, Netherlands) · 2026Review
- The regulatory roles of dysregulated lactate dehydrogenase A in anti-tumor immunity within immune cells.Frontiers in immunology · 2026Review
- Unraveling autophagy-metabolism crosstalk in cancer: Molecular insights and therapeutic strategies.Theranostics · 2026Review
- Metabolic adaptations in cancer progression.Physiological reviews · 2026Review
- Prognostic Factors Analysis in Patients with Hepatocellular Carcinoma Receiving PD-1/PD-L1 Inhibitors.Journal of hepatocellular carcinoma · 2026Article
- The Interdependence of Carbon Substrates and Metabolic Pathways Enables the Metabolic Plasticity of Cancer Cells.Advances in experimental medicine and biology · 2026Review
- N-acetylcysteine restores osteogenesis in human periodontal ligament stem cells by attenuating HIF-1α-driven oxidative stress and glycolytic reprogramming.Journal of dental sciences · 2026Article
- AARS1-mediated AKR1B10 lactylation stabilizes an aerobic glycolysis-positive feedback loop to drive lenvatinib resistance in hepatocellular carcinoma.Clinical and translational medicine · 2026Article
- CDCP1/mitochondrial Src axis increases electron transport chain function to promote metastasis in triple-negative breast cancer.British journal of cancer · 2025Article
- CDK1-mediated phosphorylation of LDHA fuels mitosis through LDHB-dependent lactate oxidation.EMBO reports · 2025Article
- Targeting LINC01711 in FAPCell death & disease · 2025Article
122 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
12 authors at 2 institutions in 1 country.
Funding
Abstract
Metastases remain the major cause of death from cancer. Recent molecular advances have highlighted the importance of metabolic alterations in cancer cells, including the Warburg effect that describes an increased glycolysis in cancer cells. However, how this altered metabolism contributes to tumour metastasis remains elusive. Here, we report that phosphorylation-induced activation of lactate dehydrogenase A (LDHA), an enzyme that catalyses the interconversion of pyruvate and lactate, promotes cancer cell invasion, anoikis resistance and tumour metastasis. We demonstrate that LDHA is phosphorylated at tyrosine 10 by upstream kinases, HER2 and Src. Targeting HER2 or Src attenuated LDH activity as well as invasive potential in head and neck cancer and breast cancer cells. Inhibition of LDH activity by small hairpin ribonucleic acid or expression of phospho-deficient LDHA Y10F sensitized the cancer cells to anoikis induction and resulted in attenuated cell invasion and elevated reactive oxygen species, whereas such phenotypes were reversed by its product lactate or antioxidant N-acetylcysteine, suggesting that Y10 phosphorylation-mediated LDHA activity promotes cancer cell invasion and anoikis resistance through redox homeostasis. In addition, LDHA knockdown or LDHA Y10F rescue expression in human cancer cells resulted in decreased tumour metastasis in xenograft mice. Furthermore, LDHA phosphorylation at Y10 positively correlated with progression of metastatic breast cancer in clinical patient tumour samples. Our findings demonstrate that LDHA phosphorylation and activation provide pro-invasive, anti-anoikis and pro-metastatic advantages to cancer cells, suggesting that Y10 phosphorylation of LDHA may represent a promising therapeutic target and a prognostic marker for metastatic human cancers.
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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 Socratic graph.