Scattered DUSP28 is a novel biomarker responsible for aggravating malignancy via the autocrine and paracrine signaling in metastatic pancreatic cancer

摘要

Pancreatic cancer remains one of the most dangerous cancers with a grave prognosis. We have reported that dual specificity phosphatise 28 (DUSP28) could be secreted in pancreatic cancer cells. However, its biological function is poorly understood. Here, we distinguish the function of scattered DUSP28 in human pancreatic cancer. DUSP28 was specifically secreted to cultured medium in metastatic pancreatic cancer cells. Treatment with recombinant DUSP28 significantly increased the migration, invasion, and viability of metastatic pancreatic cancer cells through the activation of CREB, AKT, and ERK1/2 signaling pathways. In addition, administration of recombinant DUSP28 elicited pro-angiogenic effects in human umbilical vein endothelial cells. Injection of recombinant DUSP28 also produced tumor growth in vivo. Of interest, DUSP28 formed an autocrine loop with integrin al (ITG alpha 1) by transcriptional regulation and recombinant DUSP28 acted as an oncogenic reagent through the interaction with ITG alpha 1. Notably, scattered DUSP28 could be detected in whole blood samples of pancreatic cancer patients by accessible immunoassay. These results provide the basis for DUSP28 as a promising therapeutic target and a biomarker for metastatic pancreatic cancer.