期刊
CELLULAR AND MOLECULAR LIFE SCIENCES
卷 77, 期 2, 页码 305-321出版社
SPRINGER BASEL AG
DOI: 10.1007/s00018-019-03278-z
关键词
Warburg effect; Mitochondrial respiration; Tumor microenvironment; Epithelial-mesenchymal transition; Metastatic niche; Hybrid metabolic phenotype
资金
- Non-profit Central Research Institute Fund of Chinese Academy of Medical Sciences [2018PT32014]
- CAMS Innovation Fund for Medical Sciences (CIFMS) [2016-I2 M-1-001]
- National Nature Science Foundation of China [81672960, 81672443]
Pancreatic ductal adenocarcinoma is prone to distant metastasis and is expected to become the second leading cause of cancer-related death. In an extremely nutrient-deficient and hypoxic environment resulting from uncontrolled growth, vascular disturbances and desmoplastic reactions, pancreatic cancer cells utilize metabolic reprogramming to satisfy their energy demand and support malignant behaviors such as metastasis. Notably, pancreatic cancer cells show extensive enhancement of glycolysis, including glycolytic enzyme overexpression and increased lactate production, and this is caused by mitochondrial dysfunction, cancer driver genes, specific transcription factors, a hypoxic tumor microenvironment and stromal cells, such as cancer-associated fibroblasts and tumor-associated macrophages. The metabolic switch from oxidative phosphorylation to glycolysis in pancreatic cancer cells regulates the invasion-metastasis cascade by promoting epithelial-mesenchymal transition, tumor angiogenesis and the metastatic colonization of distant organs. In addition to aerobic glycolysis, oxidative phosphorylation also plays a critical role in pancreatic cancer metastasis in ways that remain unclear. In this review, we expound on the intracellular and extracellular causes of the enhancement of glycolysis in pancreatic cancer and the strong association between glycolysis and cancer metastasis, which we expect will yield new therapeutic approaches targeting cancer metabolism.
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