Blockade of dual-specificity phosphatase 28 decreases chemoresistance and migration in human pancreatic cancer cells

Abstract

Pancreatic cancer remains one of the most deadly cancers, with a grave prognosis. Despite numerous endeavors to improve treatment of the neoplasm, limited progress has been made. In the present study, we investigated the role of dual specificity phosphatase 28 (DUSP28) in relation to anti-cancer drug sensitivity and migratory activity in human pancreatic cancer cells for the first time. Analysis using Universal exPress Codes (UPCs) with the GEO database showed significantly higher DUSP28 mRNA expression in pancreatic cancers. We found that DUSP28 was highly expressed in several human pancreatic cancer cell lines that showed resistance to anti-cancer drugs. Overexpression of DUSP28 decreased anti-cancer drug-sensitivity and enhanced cellular migration via the ERK1/2 pathway in DUSP28-negative cell lines. Knockdown of DUSP28 re-sensitized cells to anti-cancer drugs even at sublethal doses by inducing an apoptotic pathway and significantly reduced migration in DUSP28-positive human pancreatic cancer cell lines. Furthermore, DUSP28-positive cell line (Panc-1) xenograft models were more resistant to gemcitabine treatment than DUSP28-negative cell line (SNU-213) xenograft models. Collectively, these results indicate that DUSP28 plays a key role in drug resistance and migratory activity in human pancreatic cells, and suggest that targeting DUSP28 might have clinical relevance in eradicating malignant pancreatic cancers.