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

Chu An Wang, I. Heng Chang, Pei Chi Hou, Yu Jing Tai, Wan Ning Li, Pei Ling Hsu, Shang Rung Wu, Wen Tai Chiu, Chien Feng Li, Yan Shen Shan, Shaw Jenq Tsai

Research output: Contribution to journalArticlepeer-review

29 Citations (Scopus)


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.

Original languageEnglish
Article number1746529
JournalJournal of Extracellular Vesicles
Issue number1
Publication statusPublished - 2020 Jan 1

All Science Journal Classification (ASJC) codes

  • Histology
  • Cell Biology


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