Tumoral microvesicle–activated glycometabolic reprogramming in fibroblasts promotes the progression of oral squamous cell carcinoma
| Autor: | Meng Wang, Ting-Lin Yan, Hui Wang, Ke Liu, Lin Wang, Zheng-Jun Shang, Erhui Jiang, Qing Liu, Zhe Shao, Xiaocheng Zhou, Zhi Xu, Chun-Ming Huang, Yang Chen |
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| Rok vydání: | 2019 |
| Předmět: |
Monocarboxylic Acid Transporters
0301 basic medicine Stromal cell MAP Kinase Signaling System Caveolin 1 Cell Mice Nude Biochemistry Mice 03 medical and health sciences 0302 clinical medicine Cancer-Associated Fibroblasts Cell Line Tumor Tumor Microenvironment Genetics medicine Animals Humans Reverse Warburg effect Lactic Acid Molecular Biology Mice Inbred BALB C Tumor microenvironment Chemistry Microvesicle Fibroblasts Coculture Techniques Microvesicles Gene Expression Regulation Neoplastic 030104 developmental biology medicine.anatomical_structure Tumor progression Microvessels Carcinoma Squamous Cell Disease Progression Cancer research Female Mouth Neoplasms Stromal Cells Glycolysis Reprogramming 030217 neurology & neurosurgery Biotechnology |
| Zdroj: | The FASEB Journal. 33:5690-5703 |
| ISSN: | 1530-6860 0892-6638 |
| DOI: | 10.1096/fj.201802226r |
| Popis: | Metabolic reprogramming is a hallmark of cancer. Stromal cells could function as providers of energy metabolites for tumor cells by undergoing the "reverse Warburg effect," but the mechanism has not been fully elucidated. The interaction between the tumoral microvesicles (TMVs) and stroma in the tumor microenvironment plays a critical role in facilitating cancer progression. In this study, we demonstrated a novel mechanism for the TMV-mediated glycometabolic reprogramming of stromal cells. After being incubated with TMVs, normal human gingival fibroblasts exhibited a phenotype switch to cancer-associated fibroblasts and underwent a degradation of caveolin 1 (CAV1) through the ERK1/2-activation pathway. CAV1 degradation further induced the metabolic switch to aerobic glycolysis in the fibroblasts. The microvesicle-activated fibroblasts absorbed more glucose and produced more lactate. The migration and invasion of oral squamous cell carcinoma (OSCC) were promoted after being cocultured with the activated fibroblasts. Fibroblast-cancer cell glycometabolic coupling ring mediated by monocarboxylate transporter (MCT) 4 and MCT1 was then proved in the tumor microenvironment. Results indicated a mechanism for tumor progression by the crosstalk between tumor cells and stromal cells through the reverse Warburg effect via TMVs, thereby identifying potential targets for OSCC prevention and treatment.-Jiang, E., Xu, Z., Wang, M., Yan, T., Huang, C., Zhou, X., Liu, Q., Wang, L., Chen, Y., Wang, H., Liu, K., Shao, Z., Shang, Z. Tumoral microvesicle-activated glycometabolic reprogramming in fibroblasts promotes the progression of oral squamous cell carcinoma. |
| Databáze: | OpenAIRE |
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