Human CPTP 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 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.

• Authors: Yanqun Zhang, Shenying Ji, Xiangyu Zhang, Mengyun Lu, Yihong Hu, Yucheng Han, Guanghou Shui, Sin Man Lam, Xianqiong Zou
• Journal: International journal of biological sciences (Int J Biol Sci) Vol. 18 Issue 13 Pg. 4963-4983 ( 2022) ISSN: 1449-2288 [Electronic] Australia
• PMID: 35982909 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © The author(s).

Chemical References

• CPTP protein, human
• Ceramides
• Minor Histocompatibility Antigens
• Phospholipid Transfer Proteins
• Sphingolipids
• Phosphotransferases (Alcohol Group Acceptor)
• phosphatidylinositol phosphate 4-kinase
• Proto-Oncogene Proteins c-akt

Topics

• Cell Line, Tumor
• Cell Movement
• Cell Proliferation (genetics)
• Ceramides
• Epithelial-Mesenchymal Transition (genetics)
• Gene Expression Regulation, Neoplastic
• Humans
• Minor Histocompatibility Antigens (metabolism)
• Pancreatic Neoplasms (pathology)
• Phospholipid Transfer Proteins (genetics)
• Phosphotransferases (Alcohol Group Acceptor) (metabolism)
• Proto-Oncogene Proteins c-akt (metabolism)
• Sphingolipids (metabolism)