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

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 CPTP in PC have not been clarified. In this study, by RT-qPCR and immunohistochemistry analysis, we found that CPTP 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 in vitro, as well as xenograft model assays in vivo, we further proved that CPTP enhanced PC cells growth and metastasis. In PC cells, human CPTP 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 CPTP expression in PC cells. Collectively, these findings suggested that CPTP may function as a pro-tumorigenic gene in PC cells and could be a promising therapeutic target in PC.

Human cathelicidin antimicrobial peptide suppresses proliferation, migration and invasion of oral carcinoma HSC-3 cells via a novel mechanism involving caspase-3 mediated apoptosis.

Human cathelicidin antimicrobial peptide and its active product, LL­37 (CAMP/LL­37), exhibit a broad spectrum of antimicrobial effects. An increasing number of studies have shown that human CAMP/LL­37 also serves significant roles in various types of cancer. The primary aims of the present study were to investigate the roles and mechanisms of human CAMP/LL­37 in oral squamous cell carcinoma (OSCC) cells. The results indicated that either LL­37 C­terminal deletion mutants (CDEL) or CAMP stable expression in HSC­3 cells reduced colony formation, proliferation, migration and invasion ability of the cells. Expression analysis demonstrated that either CDEL or CAMP stable expression in HSC­3 cells induced caspase­3 mediated apoptosis via the P53­Bcl­2/BAX signalling pathway, whereas the levels of cell cycle­related proteins, cyclin B1 and PKR­like ER kinase, were significantly upregulated in the CAMP, but not in the CDEL overexpressing cells. Transcriptional profile comparisons revealed that CDEL or CAMP stable expression in HSC­3 cells upregulated expression of genes involved in the IL­17­dependent pathway compared with the control. Taken together, these results suggest that CAMP may act as a tumour suppressor in OSCC cells, and the underlying mechanism involves the induction of caspase­3 mediated apoptosis via the P53­Bcl­2/BAX signalling pathway.