Autocrine DUSP28 signaling mediates pancreatic cancer malignancy via regulation of PDGF-A

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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.
Publisher
NATURE PUBLISHING GROUP
Issue Date
2017-10
Language
English
Article Type
Article
Keywords

ENDOTHELIAL GROWTH-FACTOR; DUAL-SPECIFICITY PHOSPHATASES; TUMOR-GROWTH; CELLS; INHIBITION; VEGF; ADENOCARCINOMA; ANGIOGENESIS; EXPRESSION; MIGRATION

Citation

SCIENTIFIC REPORTS, v.7

ISSN
2045-2322
DOI
10.1038/s41598-017-13023-w
URI
http://hdl.handle.net/10203/226710
Appears in Collection
BiS-Journal Papers(저널논문)
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