ArticleClinical and translational medicine2021
Functional inhibition of lactate dehydrogenase suppresses pancreatic adenocarcinoma progression.
Article in Clinical and translational medicine, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
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43 citing papers in PubMed, 69 citations in OpenAlex.
- An externally validated lactylation-associated prognostic signature for overall survival prediction in lung adenocarcinoma identifiesTranslational cancer research · 2026Article
- Ldha Regulates Osteosarcoma Lung Metastasis through Hedgehog Signaling.Cancer research communications · 2026Article
- Global profiling of protein lactylation in pancreatic ductal adenocarcinoma.Scientific reports · 2026Article
- The moonlighting functions of glycolytic enzymes in tumorigenesis.Cellular oncology (Dordrecht, Netherlands) · 2026Review
- Glycolytic heterogeneity drives metabolic-targeted therapy in pancreatic ductal adenocarcinoma.Signal transduction and targeted therapy · 2026Article
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- The integration of single-cell and metabolomics reveals the increase of oxidative phosphorylation during the liver metastasis of colorectal cancer.Cancer & metabolism · 2025Article
- Burning lactic acid: a road to revitalizing antitumor immunity.Frontiers of medicine · 2025Review
- L- and D-Lactate: unveiling their hidden functions in disease and health.Cell communication and signaling : CCS · 2025Review
- Multi-omics profiling identifies berberine and salidroside as potential immunoregulatory compounds in radiation-induced skin injury.Frontiers in immunology · 2025Article
- The lactylation-macrophage interplay: implications for gastrointestinal disease therapeutics.Frontiers in immunology · 2025Review
- Reprogramming of glucose metabolism in pancreatic cancer: mechanisms, implications, and therapeutic perspectives.Frontiers in immunology · 2025Review
- Pathomic and bioinformatics analysis of clinical-pathological and genomic factors for pancreatic cancer prognosis.Scientific reports · 2024Article
- Glycolysis-mTORC1 crosstalk drives proliferation of patient-derived endometrial cancer spheroid cells with ALDH activity.Cell death discovery · 2024Article
- Mechanisms of Berberine in anti-pancreatic ductal adenocarcinoma revealed by integrated multi-omics profiling.Scientific reports · 2024Article
- Vitamin-C-dependent downregulation of the citrate metabolism pathway potentiates pancreatic ductal adenocarcinoma growth arrest.Molecular oncology · 2024Article
- Article
- Berberine chloride suppresses pancreatic adenocarcinoma proliferation and growth by targeting inflammation-related genes: an in silico analysis with in vitro and vivo validation.Cancer chemotherapy and pharmacology · 2024Article
- NOTCH3 as a prognostic biomarker and its correlation with immune infiltration in gastrointestinal cancers.Scientific reports · 2024Article
- Inhibition of Nogo-B reduces the progression of pancreatic cancer by regulation NF-κB/GLUT1 and SREBP1 pathways.iScience · 2024Article
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundPancreatic adenocarcinoma (PAAD) a highly lethal malignancy. The current use of clinical parameters may not accurately predict the clinical outcome, which further renders the unsatisfactory therapeutic outcome.
methodsIn this study, we retrospectively analyzed the clinical-pathological characteristics and prognosis of 253 PAAD patients. Univariate, multivariate, and Kaplan-Meier survival analyses were conducted to assess risk factors and clinical outcomes. For functional study, we performed bidirectional genetic manipulation of lactate dehydrogenase A (LDHA) in PAAD cell lines to measure PAAD progression by both in vitro and in vivo assays.
resultsLDHA is particularly overexpressed in PAAD tissues and elevated serum LDHA-transcribed isoenzymes-5 (LDH-5) was associated with poorer patients' clinical outcomes. Genetic overexpression of LDHA promoted the proliferation and invasion in vitro, and tumor growth and metastasis in vivo in murine PAAD orthotopic models, while knockdown of LDHA exhibited opposite effects. LDHA-induced L-lactate production was responsible for the LDHA-facilitated PAAD progression. Mechanistically, LDHA overexpression reduced the phosphorylation of metabolic regulator AMPK and promoted the downstream mTOR phosphorylation in PAAD cells. Inhibition of mTOR repressed the LDHA-induced proliferation and invasion. A natural product berberine was selected as functional inhibitor of LDHA, which reduced activity and expression of the protein in PAAD cells. Berberine inhibited PAAD cells proliferation and invasion in vitro, and suppressed tumor progression in vivo. The restoration of LDHA attenuated the suppressive effect of berberine on PAAD.
conclusionsOur findings suggest that LDHA may be a novel biomarker and potential therapeutic target of human PAAD.
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