ArticleCancer biology & therapy2024
Hypoxia promotes non-small cell lung cancer cell stemness, migration, and invasion via promoting glycolysis by lactylation of SOX9.
Article in Cancer biology & therapy, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 81 papers.
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81 citing papers in PubMed, 76 citations in OpenAlex.
- Neurexophilin 4 facilitates the malignant progression of kidney renal clear cell carcinoma by regulating PI3K/AKT-mediated glycolysis.Molecular genetics and genomics : MGG · 2026Article
- Review
- Next-generation oncolytic virotherapy for lung cancer: bridging innovative vector engineering with clinical immunotherapy.Translational lung cancer research · 2026Review
- Unveiling Lactylation: A Novel Frontier in Cancer Stemness and Therapy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Cancer stem cell plasticity: mechanisms, immune microenvironment crosstalk, and therapeutic implications.Journal of hematology & oncology · 2026Review
- Protein lactylation in health and diseases: molecular mechanisms, biological significance, and clinical implications.Signal transduction and targeted therapy · 2026Review
- Impact of mitochondrial reductive stress due to respiratory chain limitation on cancer via posttranslational modifications.Redox biology · 2026Review
- DHX9 transcriptional upregulation and lactylation at K1024 fuels a glycolysis-histone lactylation loop in osteosarcoma.Journal of translational medicine · 2026Article
- Unveiling lactylation: A novel frontier in the pathogenesis of diabetic nephropathy (Review).International journal of molecular medicine · 2026Review
- SLC27A1 overexpression correlates with lactylation and poor colorectal cancer progression.Scientific reports · 2026Article
- Lactate and lactylation: mechanisms, function, diseases, and therapeutic targets.Molecular biomedicine · 2026Review
- LDHC4 drives lung adenocarcinoma progression by inducing lactylation of RB1 at lysine 900 to disrupt the RB1-E2F1 complex.Journal of translational medicine · 2026Article
- Role and clinical importance of lactylation in tumors (Review).Molecular medicine reports · 2026Review
- Defining the tumor microenvironment of non-small cell lung cancer.Immunology and cell biology · 2026Review
- Development and validation of an interpretable prognostic model for bladder cancer based on lactylation associated genes using SHAP analysis.Discover oncology · 2026Article
- Article
- ZFP36L1 promotes non-small cell lung cancer progression under hypoxia by modulating CXCL9:SPP1 polarity: A single-cell transcriptomic study.Clinical and translational medicine · 2026Article
- LDHA-Mediated H3K18 Lactylation Promotes the Glycolysis in Non-Small Cell Lung Cancer Through Targeting PTEN.Biochemical genetics · 2026Article
- Lactylation and acetylation: parallel paths, divergent deeds, and research dilemmas.Journal of translational medicine · 2026Review
- Lactylation as a metabolic-epigenetic switch in cancer: dual roles in cell death resistance and therapeutic vulnerability.Cell death & disease · 2026Review
21 more citing papers are in PubMed but not listed here.
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundLung cancer is the deadliest form of malignancy and the most common subtype is non-small cell lung cancer (NSCLC). Hypoxia is a typical feature of solid tumor microenvironment. In the current study, we clarified the effects of hypoxia on stemness and metastasis and the molecular mechanism.
methodsThe biological functions were assessed using the sphere formation assay, Transwell assay, and XF96 extracellular flux analyzer. The protein levels were detected by western blot. The lactylation modification was assessed by western blot and immunoprecipitation. The role of SOX9 in vivo was explored using a xenografted tumor model.
resultsWe observed that hypoxia promoted sphere formation, migration, invasion, glucose consumption, lactate production, glycolysis, and global lactylation. Inhibition of glycolysis suppressed cell stemness, migration, invasion, and lactylation. Moreover, hypoxia increased the levels of SOX9 and lactylation of SOX9, whereas inhibition of glycolysis reversed the increase. Additionally, knockdown of SOX9 abrogated the promotion of cell stemness, migration, and invasion. In tumor-bearing mice, overexpression of SOX9 promoted tumor growth, and inhibition of glycolysis suppressed tumor growth.
conclusionHypoxia induced the lactylation of SOX9 to promote stemness, migration, and invasion via promoting glycolysis. The findings suggested that targeting hypoxia may be an effective way for NSCLC treatment and reveal a new mechanism of hypoxia in NSCLC.
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