Dataset Information


DUSP2 regulates extracellular vesicle-VEGF-C secretion and pancreatic cancer early dissemination.

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.


PROVIDER: S-EPMC7170376 | BioStudies | 2020-01-01

REPOSITORIES: biostudies

Similar Datasets

2018-01-01 | S-EPMC6057920 | BioStudies
2014-01-01 | S-EPMC4462390 | BioStudies
2019-01-01 | S-EPMC6713506 | BioStudies
2020-01-01 | S-EPMC6942436 | BioStudies
2017-01-01 | S-EPMC5601918 | BioStudies
2012-01-01 | S-EPMC3262079 | BioStudies
2012-01-01 | S-EPMC3464270 | BioStudies
2020-01-01 | S-EPMC7281335 | BioStudies
2017-01-01 | S-EPMC5422112 | BioStudies
2019-01-01 | S-EPMC6383691 | BioStudies