Novel Protein CPTP Offers Hope for Treatment of Cancer and Other Diseases

According to a team of researchers from the United States, Russia and Spain, the discovery of a new protein, named ceramide-1 phosphate transport protein, could lead to the development of new drugs to treat a variety of cancers and other diseases.

Left, center: structure of CPTP. Right: surface electrostatics of CPTP showing positive-, blue, and negative-, red, charged residues (Simanshu DK et al).

Left, center: structure of CPTP. Right: surface electrostatics of CPTP showing positive-, blue, and negative-, red, charged residues (Simanshu DK et al).

The scientists discovered that the ceramide-1 phosphate transport protein (CPTP) regulates levels of biologically active lipids, which are molecules such as fatty acids that often play a role in cell signaling.

They found that CPTP’s main function is to transport ceramide-1-phosphate (C1P), a lipid that helps regulate cell growth, survival, migration and inflammation. Specifically, C1P increases the production of pro-inflammatory eicosanoids – powerful signaling molecules that contribute to chronic inflammation in diseases such as cancer, asthma, atherosclerosis and thrombosis – and the discovery of CPTP sheds a light on the cellular mechanisms that contribute to these diseases.

“We may have identified the newest target for treating cancer. Because of the important role this protein plays in a number of cellular functions, it could also have large implications for a variety of diseases like cancer that are caused by inflammation,” explained Prof Charles Chalfant of the Virginia Commonwealth University, co-author of a study published in the journal Nature.

The team was able to determine the composition of the bioactive lipids regulated by CPTP. Residing in the cytosol, or the liquid within cells, the scientists found that CPTP regulates catabolism of C1P, a process that breaks down the molecule in order to release its energy. They also demonstrated that CPTP transports C1P to the cellular membrane where it helps synthesize eicosanoids from fatty acids in the membrane.

The scientists provided further proof that C1P regulates group IVA phospholipase A2, an enzyme that promotes inflammation through the production of a fatty acid known as arachidonic acid. The release of arachidonic acid via C1P activation of this enzyme was shown to trigger the production of eicosanoids. These findings help to explain the reported link between ceramide kinase, the enzyme responsible for C1P production, and poor prognosis in breast cancer patients, which further suggests that alleviation of systemic inflammation may lead to better prognosis and better treatment responses.

“Moving forward, we hope to use our knowledge of the structure of CPTP in order to find small molecules and other means that can block it,” Prof Chalfant said.

“The immediate uses of such therapeutics might be to restore clotting in trauma patients by maintaining the levels of specific eicosanoids that mediate blood clotting. However, with further research we hope to define exactly how CPTP is produced so that we can regulate its production and potentially develop new treatments for a variety of diseases.”

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Bibliographic information: Simanshu DK et al. Non-vesicular trafficking by a ceramide-1-phosphate transfer protein regulates eicosanoids. Nature, published online July 17, 2013; doi: 10.1038/nature12332