Pancreatic ductal adenocarcinoma (PDAC) is one of the most fatal cancers of the digestive system. Despite the development of novel therapeutic methods, including chemotherapy, radiotherapy, and molecular targeted therapy, the incidence rate of PDAC is almost equal to the mortality rate with 5-year overall survival rate less than 5%. Kras mutation is found in 95% of patient with PDAC specimens, but targeting Kras mutation do not benefit patients with pancreatic cancer in preclinical trials. c-Myc is one of the main effector molecules of the Kras signaling pathway. In this study, we found that dysregulation of FAST kinase-domain-containing protein 2 (FASTKD2) resulted in the poor prognosis of patients with PDAC. Then, we showed that FASTKD2 promoted pancreatic cancer cell proliferation and invasion. Importantly, we demonstrated that c-Myc was transcriptionally increased by FASTKD2/BRD4 axis and responsible for FASTKD2-mediated tumor growth and invasion in pancreatic cancer cells. Collectively, this study uncovered that FASTKD2 promoted cancer cell progression through upregulating Myc expression in pancreatic cancer. FASTKD2 might be a potential target for pancreatic cancer therapy.
Keywords: FAST kinase-domain-containing protein 2; c-Myc; cell invasion; cell proliferation; pancreatic ductal adenocarcinoma.
© 2019 Wiley Periodicals, Inc.