Pancreatic Tumorigenesis: Oncogenic KRAS and the Vulnerability of the Pancreas to Obesity
Abstract
Simple Summary
Abstract
1. Introduction
2. Roles of Obesity in the Development of PDAC
3. Roles of Oncogenic KRAS in the Development of PDAC
4. Interplay between Obesogenic HFD, Inflammation, and Oncogenic KRAS in PDAC Development
5. FGF21: A Potential Missing Link between Obesity/Inflammation and Mutant KRAS-mediated Pancreatic Tumorigenesis
6. Concluding Remarks and Future Perspectives
Author Contributions
Funding
Conflicts of Interest
References
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FGF21-Related Models | Mouse Genotype | Phenotype or Effects | Reference |
---|---|---|---|
FGF21 overexpression | ApoECre-FGF21Tg | Protects acinar cells from caerulein, mechanical, or thapsigargin induced pancreatitis and stress damage. | [146] |
Protects acinar cells from caerulein, mechanical, or thapsigargin induced pancreatitis and stress damage. | [148] | ||
Reduces β-cell apoptosis in db/db mice. | [149] | ||
Mitigates acinar damage of Mist1−/− pancreas. | [156] | ||
FGF21 knockout | Whole-body or germline FGF21−/− | Whole-body or germline FGF21−/− | [146] |
Exacerbates palmitate-induced pancreatic β-cell failure. | [149] | ||
Increases zymogen granules and susceptibility to ER stress in acinar cells. | [148] | ||
Induces insulin resistance, pancreatic islet hyperplasia, and dysfunction. | [158] | ||
Acinar cell-specific KLB−/− | KlbCela1-/- | Increases zymogen granules in acinar cells. | [148] |
Injection of FGF21 | WT KRASLSL-G12D/+ | Inhibits pancreatitis and fibrosis | [151,157] |
Compensates KRAS induced FGF21 loss to inhibit pancreatic inflammation, fibrosis, PanIN lesion, and PDAC development | [53] | ||
Injection ofF GF21 | Streptozotocin [STZ]-induced type 1 diabetes | Improves islet engraftment and insulin sensitivity. | [154] |
Prevents the increase in glycemia and lowers lipids. | [159] | ||
Injection of FGF21 | ob/ob and DIO | Improves glucose tolerance and insulin sensitivity, but has no direct effect on islet insulin secretion. | [155] |
Injection of FGF21 or analogs | db/db | Improves islet survival and function, insulin sensitivity and glucose homeostasis. | [150,160] |
Increases pancreatic β-cell mass | [161] |
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Luo, Y.; Li, X.; Ma, J.; Abbruzzese, J.L.; Lu, W. Pancreatic Tumorigenesis: Oncogenic KRAS and the Vulnerability of the Pancreas to Obesity. Cancers 2021, 13, 778. https://doi.org/10.3390/cancers13040778
Luo Y, Li X, Ma J, Abbruzzese JL, Lu W. Pancreatic Tumorigenesis: Oncogenic KRAS and the Vulnerability of the Pancreas to Obesity. Cancers. 2021; 13(4):778. https://doi.org/10.3390/cancers13040778
Chicago/Turabian StyleLuo, Yongde, Xiaokun Li, Jianjia Ma, James L. Abbruzzese, and Weiqin Lu. 2021. "Pancreatic Tumorigenesis: Oncogenic KRAS and the Vulnerability of the Pancreas to Obesity" Cancers 13, no. 4: 778. https://doi.org/10.3390/cancers13040778
APA StyleLuo, Y., Li, X., Ma, J., Abbruzzese, J. L., & Lu, W. (2021). Pancreatic Tumorigenesis: Oncogenic KRAS and the Vulnerability of the Pancreas to Obesity. Cancers, 13(4), 778. https://doi.org/10.3390/cancers13040778