DRP1 upregulation promotes pancreatic cancer growth and metastasis through increased aerobic glycolysis
- PMID: 31674061
- DOI: 10.1111/jgh.14912
DRP1 upregulation promotes pancreatic cancer growth and metastasis through increased aerobic glycolysis
Erratum in
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Corrigendum.J Gastroenterol Hepatol. 2022 Jun;37(6):1170. doi: 10.1111/jgh.15831. J Gastroenterol Hepatol. 2022. PMID: 35702823 No abstract available.
Abstract
Background: Mitochondrial shape is dynamically changed by fusion and fission processes in cells, and dysfunction of this process has become one of the emerging hallmarks of cancer. However, the expression patterns and biological effects of mitochondrial fission and fusion proteins in pancreatic cancer (PC) are still unclear.
Methods: The expressions of mitochondrial fission and fusion proteins were first evaluated by quantitative reverse transcription polymerase chain reaction and western blot analysis in both PC cell lines and tissue samples. In addition, the biologic functions of the differentially expressed proteins in PC cell growth and metastasis both in vitro and in vivo and their potential underlying mechanisms were systematically explored.
Results: We first found that DRP1 was substantially upregulated in PC cell lines and tissue samples mainly due to the downregulation of miR-29a, which contributed to the poor survival of PC patients. DRP1 promoted the growth and metastasis of PC cells both in vitro and in vivo by inducing G1-S cell cycle transition and matrix metalloproteinase 2 secretion. Mechanistic investigations revealed that increased DRP1 upregulation-mediated mitochondrial fission and subsequently enhanced aerobic glycolysis were involved in the promotion of growth and metastasis by DRP1 in PC cells.
Conclusions: Our findings demonstrate that mitochondrial fusion protein DRP1 plays a critical oncogenic role in PC cells by enhancing aerobic glycolysis, which could serve as a novel therapeutic target for PC treatment.
Keywords: DRP1; Glycolysis; Growth; Metastasis; Mitochondrial dynamics; Pancreatic cancer.
© 2019 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.
References
-
- Kamisawa T, Wood LD, Itoi T, Takaori K. Pancreatic cancer. Lancet 2016; 388: 73-85.
-
- Wolfgang CL, Herman JM, Laheru DA et al. Recent progress in pancreatic cancer. CA Cancer J. Clin. 2013; 63: 318-348.
-
- Strobel O, Neoptolemos J, Jager D, Buchler MW. Optimizing the outcomes of pancreatic cancer surgery. Nat. Rev. Clin. Oncol. 2018; 16: 11-26.
-
- Ko AH. Progress in the treatment of metastatic pancreatic cancer and the search for next opportunities. J. Clin. Oncol. 2015; 33: 1779-1786.
-
- Friedman JR, Nunnari J. Mitochondrial form and function. Nature 2014; 505: 335-343.
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