Contribution of DUSP28 to Regulation of Mucins in Human Pancreatic Cancer Cells

Abstract

Pancreatic cancer remains one of the most deadly cancers, and once diagnosed, the prognosis for patient survival is poor. Patient outcomes have not been improved despite considerable and continuous efforts. We have suggested that dual-specificity phosphatase 28 (DUSP28) is a potential anti-cancer target to inhibit malignant pancreatic cancers. In this context, atypical DUSP28 can affect the regulation of mucins such as mucin5B (MUC5B) and mucin16 (MUC16). To investigate this correlation, we analysed mRNA levels of DUSP28 and mucins using the Gene Expression Omnibus public microarray database in pancreatic cancer, which indicated higher DUSP28, MUC1, MUC4, MUC5B, MUC16 and MUC20 mRNA levels in pancreatic cancers compared with normal pancreas tissue. In addition, DUSP28 expression in human pancreatic cancers correlated positively with those of MUC1, MUC4, MUC5B, MUC16 and MUC20. In contrast, there were no significant correlations between DUSP28 and mucins in normal pancreas tissues. Decreased DUSP28 expression resulted in down regulation of MUC5B and MUC16 at both the mRNA and protein levels. Furthermore, blockade of MUC5B or MUC16 expression inhibited migration and survival of cancer cells through the inhibition of phosphorylated FAK and ERK1/2. Collectively, we propose that DUSP28 uniquely links regulation of MUC5B and MUC16 to migration and survival of pancreatic cancer cells, which strongly support a rationale for targeting DUSP28 to inhibit development of malignant pancreatic cancer.