Human <i>CPTP</i> promotes growth and metastasis via sphingolipid metabolite ceramide and PI4KA/AKT signaling in pancreatic cancer cells

Abstract

Pancreatic cancer (PC) is a devastating solid malignancy with a dismal prognosis. The treatment of metastatic PC is a current challenge for medical oncologists due to a lack of early detection, drug resistance, and relapse. Therefore, potential biomarkers and effective therapeutic targets for PC are urgently required. Ceramide-1-phosphate transfer protein (CPTP) is a member of the glycolipid transfer protein family, which is associated with autophagy and inflammation regulation. The roles and mechanisms of <i>CPTP</i> in PC have not been clarified. In this study, by RT-qPCR and immunohistochemistry analysis, we found that <i>CPTP</i> is highly expressed in PC and is associated with a poor prognosis in PC patients. By using cell counting kit-8, colony formation, transwell and matrigel assays <i>in vitro</i>, as well as xenograft model assays <i>in vivo</i>, we further proved that <i>CPTP</i> enhanced PC cells growth and metastasis. In PC cells, human <i>CPTP</i> promotes growth and metastasis via sphingolipid metabolite ceramide and PI4KA/AKT signaling. Sp (specific protein)-1 and Sp3 transcription factors also act as upstream positive regulators of <i>CPTP</i> expression in PC cells. Collectively, these findings suggested that <i>CPTP</i> may function as a pro-tumorigenic gene in PC cells and could be a promising therapeutic target in PC.