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DUSP2 regulates extracellular vesicle-VEGF-C secretion and pancreatic cancer early dissemination.
- Source :
- Journal of Extracellular Vesicles; Dec2020, Vol. 9 Issue 1, p1-10, 10p
- Publication Year :
- 2020
-
Abstract
- Early dissemination is a unique characteristic and a detrimental process of pancreatic ductal adenocarcinoma (PDAC); however, the underlying mechanism remains largely unknown. Here, we investigate the role of dual-specificity phosphatase-2 (DUSP2)-vascular endothelial growth factor-C (VEGF-C) axis in mediating PDAC lymphangiogenesis and lymphovascular invasion. Expression of DUSP2 is greatly suppressed in PDAC, which results in increased aberrant expression of extracellular vesicle (EV)-associated VEGF-C secretion. EV-VEGF-C exerts paracrine effects on lymphatic endothelial cells and autocrine effects on cancer cells, resulting in the lymphovascular invasion of cancer cells. Tissue-specific knockout of Dusp2 in mouse pancreas recapitulates PDAC phenotype and lymphovascular invasion. Mechanistically, loss-of-DUSP2 enhances proprotein convertase activity and vesicle trafficking to promote the release of the mature form of EV-VEGF-C. Collectively, these findings represent a conceptual advance in understanding pancreatic cancer lymphovascular invasion and suggest that loss-of-DUSP2-mediated VEGF-C processing may play important roles in early dissemination of pancreatic cancer. Abbreviations: DUSP2: dual-specificity phosphatase-2; VEGF-C: vascular endothelial growth factor-C; EV: extracellular vesicles; PDAC: pancreatic ductal adenocarcinoma; KD: knockdown [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 20013078
- Volume :
- 9
- Issue :
- 1
- Database :
- Complementary Index
- Journal :
- Journal of Extracellular Vesicles
- Publication Type :
- Academic Journal
- Accession number :
- 146243311
- Full Text :
- https://doi.org/10.1080/20013078.2020.1746529