ArticleCell & bioscience2024
CAFs-derived lactate enhances the cancer stemness through inhibiting the MST1 ubiquitination degradation in OSCC.
Article in Cell & bioscience, 2024. 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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Who cites it
14 citing papers in PubMed.
- RNF207 promotes colorectal cancer growth by regulating the Hippo-YAP pathway via enhanced MST1 ubiquitination and degradation.Journal of gastroenterology · 2026Article
- Lactate derived from CAFs mediates H3K18la in stemness gene promoters, which promotes tumor malignant phenotype formation.Molecular genetics and genomics : MGG · 2026Article
- Cancer-Associated Fibroblast-Derived Sphingosine-1-Phosphate Activates a MALL-SDC4 Axis to Facilitate Perineural Invasion in Pancreatic Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Novel patient-derived tongue squamous cell carcinoma cell lines from non-smokers: 3D and in vivo models for drug response studies.Medical oncology (Northwood, London, England) · 2026Article
- Lactate metabolism and lactylation in cancer: from pathogenesis to therapeutic advances.Signal transduction and targeted therapy · 2026Review
- Review
- Research on the Hippo Pathway in Cancer.Cells · 2026Review
- The research advances of crosstalk between cancer-associated fibroblasts and tumor cells using co-culture organoids.Cell death & disease · 2026Review
- Novel anti-tumor strategies: targeting the crosstalk between cancer stem cells and cancer-associated fibroblasts to resist drug resistance.Cancer drug resistance (Alhambra, Calif.) · 2026Review
- Lactate and lactylation in cancer: drivers of immune suppression and microenvironmental reprogramming.Experimental hematology & oncology · 2025Review
- Histone lactylation: a new target for overcoming immune evasion and therapy resistance.Medical oncology (Northwood, London, England) · 2025Review
- Role of exosomal non‑coding RNAs in cancer‑associated fibroblast‑mediated therapy resistance (Review).International journal of oncology · 2025Review
- Lactate-Mediated Crosstalk Between Tumor Cells and Cancer-Associated Fibroblasts: Mechanisms and Therapeutic Opportunities.International journal of molecular sciences · 2025Review
- Tumor Microenvironment Lactate: Is It a Cancer Progression Marker, Immunosuppressant, and Therapeutic Target?Molecules (Basel, Switzerland) · 2025Review
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9 authors.
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Abstract
backgroundCancer-associated fibroblasts (CAFs), a predominant stromal cell type in the tumor microenvironment, significantly affect the progression of oral squamous cell carcinoma (OSCC).
resultsThe specific mechanisms through which CAFs influence the cancer stem cell phenotype in OSCC are not fully understood. This study explored the effects of lactic acid produced by CAFs on the cancer stem cells (CSCs) phenotype of OSCC cells. Our results demonstrated that CAFs exhibit increased glycolysis and lactic acid production. Lactic acid treatment enhances CSCs-related markers expression, sphere formation, and clonogenic ability of OSCC cells. RNA sequencing revealed that lactic acid treatment elevates Discs Large Homolog 5 (DLG5) expression and markedly affects the Hippo pathway. Further investigation revealed that DLG5 mediates the effects of lactic acid on the CSCs phenotype. DLG5 knockdown results in elevated expression of E3 ubiquitin ligase Cullin 3, which can promote the ubiquitination and degradation of MST1, but the expression of phosphorylated MST1 remains unchanged. This leads to enhanced binding of phosphorylated MST1 to YAP1, increasing YAP1 phosphorylation and activating the Hippo pathway.
conclusionCollectively, our findings suggest that lactic acid from CAFs promotes the CSCs phenotype in OSCC through the DLG5/CUL3/MST1 axis. Therefore, targeting lactic acid exchange between CAFs and tumor cells may provide a novel therapeutic approach to suppress the CSCs phenotype in OSCC.
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