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- Title
- Autocrine DUSP28 signaling mediates pancreatic cancer malignancy via regulation of PDGF-A
- Author(s)
- J Lee; J Lee; J H Yun; C Choi; S Cho; Seung Jun Kim; J H Kim
- Bibliographic Citation
- Scientific Reports, vol. 7, pp. 12760-12760
- Publication Year
- 2017
- Abstract
- Pancreatic cancer remains one of the most deadly cancers with a grave prognosis. Despite continuous efforts to improve remedial values, limited progress has been made. We have reported that dual specificity phosphatase 28 (DUSP28) has a critical role of chemo-resistance and migration in pancreatic cancers. However, its mechanism remains unclear. Here, we further clarify the function of DUSP28 in pancreatic cancers. Analysis using a public microarray database and in vitro assay indicated a critical role of platelet derived growth factor A (PDGF-A) in pancreatic cancer malignancy. PDGF-A was positively regulated by DUSP28 expression at the mRNA and protein levels. Enhanced DUSP28 sensitized pancreatic cancer cells to exogenous PDGF-A treatment in migration, invasion, and proliferation. Transfection with siRNA targeting DUSP28 blunted the influence of administered PDGF-A by inhibition of phosphorylation of FAK, ERK1/2, and p38 signalling pathways. In addition, DUSP28 and PDGF-A formed an acquired autonomous autocrine-signaling pathway. Furthermore, targeting DUSP28 inhibited the tumor growth and migratory features through the blockade of PDGF-A expression and intracellular signaling in vivo. Our results establish novel insight into DUSP28 and PDGF-A related autonomous signaling pathway in pancreatic cancer
- ISSN
- 2045-2322
- Publisher
- Springer-Nature Pub Group
- DOI
- http://dx.doi.org/10.1038/s41598-017-13023-w
- Type
- Article
- Appears in Collections:
- Critical Diseases Diagnostics Convergence Research Center > 1. Journal Articles
- Files in This Item:
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