Details
- Autor(en) / Beteiligte
- Titel
- EGF induces epithelial-mesenchymal transition and cancer stem-like cell properties in human oral cancer cells via promoting Warburg effect
- Ist Teil von
- Oncotarget, 2017-02, Vol.8 (6), p.9557-9571
- Ort / Verlag
- United States: Impact Journals LLC
- Erscheinungsjahr
- 2017
- Link zum Volltext
- Quelle
- Free E-Journal (出版社公開部分のみ）
- Beschreibungen/Notizen
- "Warburg effect", the enhanced glycolysis or aerobic glycolysis, confers cancer cells the ability to survive and proliferate even under stressed conditions. In this study, we explored the role of epidermal growth factor (EGF) in orchestrating Warburg effect, the epithelial-mesenchymal transition (EMT) process, and the acquisition of cancer stem-like cell properties in human oral squamous cell carcinoma (OSCC) cells. Our results showed that EGF induces EMT process in OSCC cells, which correlates with the acquisition of cancer stem-like properties, including the enrichment of CD44+/CD24- population of cancer cells and an increased expression of CSC-related genes, aldehyde dehydrogenase-1 (ALDH1) and Bmi-1. We also showed that EGF concomitantly enhanced L-lactate production, while blocking glycolysis by 2-deoxy-D-glucose (2-DG) robustly reversed EGF-induced EMT process and CSC-like properties in OSCC cells. Mechanistically, we demonstrated that EGF promoted EMT process and CSC generation through EGFR/PI3K/HIF-1α axis-orchestrated glycolysis. Using an orthotopic tumor model of human OSCC (UM-SCC1) injected in the tongue of BALB/c nude mice, we showed that treatment with 2-DG in vivo significantly inhibited the metastasis of tumor cells to the regional cervical lymph nodes and reduced the expression of ALDH1 and vimentin in both in situ tumors and tumor cell-invaded regional lymph nodes. Taken together, these findings have unveiled a new mechanism that EGF drives OSCC metastasis through induction of EMT process and CSC generation, which is driven by an enhanced glycolytic metabolic program in OSCC cells.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 1949-2553eISSN: 1949-2553DOI: 10.18632/oncotarget.13771Titel-ID: cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_5354753
- Format
- –
- Schlagworte
- Aldehyde Dehydrogenase 1 Family, Animals, Antineoplastic Agents - pharmacology, Carcinoma, Squamous Cell - drug therapy, Carcinoma, Squamous Cell - metabolism, Carcinoma, Squamous Cell - pathology, CD24 Antigen - metabolism, Cell Line, Tumor, Deoxyglucose - pharmacology, Dose-Response Relationship, Drug, Epidermal Growth Factor - pharmacology, Epithelial-Mesenchymal Transition - drug effects, ErbB Receptors - agonists, ErbB Receptors - metabolism, Female, Glycolysis - drug effects, Head and Neck Neoplasms - drug therapy, Head and Neck Neoplasms - metabolism, Head and Neck Neoplasms - pathology, Humans, Hyaluronan Receptors - metabolism, Hypoxia-Inducible Factor 1, alpha Subunit - metabolism, Isoenzymes - metabolism, Lactic Acid - metabolism, Mice, Inbred BALB C, Mice, Nude, Mouth Neoplasms - drug therapy, Mouth Neoplasms - metabolism, Mouth Neoplasms - pathology, Neoplastic Stem Cells - drug effects, Neoplastic Stem Cells - metabolism, Neoplastic Stem Cells - pathology, Phenotype, Phosphatidylinositol 3-Kinase - metabolism, Polycomb Repressive Complex 1 - metabolism, Research Paper, Retinal Dehydrogenase - metabolism, Signal Transduction - drug effects, Squamous Cell Carcinoma of Head and Neck, Time Factors, Xenograft Model Antitumor Assays