The enhancement of glycolysis regulates pancreatic cancer metastasis
Open accessAbstract
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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Pancreatic ductal adenocarcinoma (PDAC) lines were chosen because cancers of the pancreas are characterized by rapid progression, invasiveness, and elevated fermentative metabolism.
“Pancreatic ductal adenocarcinoma (PDAC) lines were chosen for our study because cancers of the pancreas are characterized by rapid progression,9,10 invasiveness,11,12 and elevated fermentative metabolism.13,14,15,16”
From Dynamic IL-6R/STAT3 signaling leads to heterogeneity of metabolic phenotype in pancreatic ductal adenocarcinoma cells (2024) · cites this paper as [15]
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- Authors
- Yang, J., Ren, B., Yang, G., Wang, H., Chen, G., You, L., Zhang, T., & Zhao, Y.
- Affiliations
- Chinese Academy of Medical Sciences & Peking Union Medical College (CN)
- Corresponding author
- You, Lei
- Zhang, Taiping
- Zhao, Yupei
- Venue
- Cellular and Molecular Life Sciences
- Published
- 2019-08-20
- Volume
- 77
- Issue
- 2
- Pages
- 305-321
- ISSN
- 1420-682X (ISSN-L)
- 1420-9071
- PMC
- PMC11104916
- OpenAlex
- W2969579026
- Cited by
- 347
- References
- 16
- Citations by year
- 2026: 26 · 2025: 54 · 2024: 57 · 2023: 71 · 2022: 70 · 2021: 49 · 2020: 19 · 2019: 1
- FWCI
- 3.30
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Cellular and Molecular Life Sciences (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Non-profit Central Research Institute Fund of Chinese Academy of Medical Sciences (2018PT32014)
- CAMS Innovation Fund for Medical Sciences (2016-I2M-1-001)
- National Natural Science Foundation of China (81672960)
- National Nature Science Foundation of China (81672443)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
- Health Sciences › Medicine › Oncology › Pancreatic and Hepatic Oncology Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Keywords
- pancreatic ductal adenocarcinoma, glycolysis, metastasis, metabolic reprogramming, aerobic glycolysis, oxidative phosphorylation, tumor hypoxia, tumor microenvironment, cancer-associated fibroblasts, tumor-associated macrophages, epithelial-mesenchymal transition, tumor angiogenesis, invasion-metastasis cascade, cancer metabolism
- MeSH terms
- Animals, Glycolysis, Humans, Neoplasm Metastasis, Neovascularization, Pathologic, Pancreatic Neoplasms, Epithelial-Mesenchymal Transition, Tumor Microenvironment
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