| credits:
In
cancer research, discovering a new protein that plays a role in cancer
is like finding a key and a treasure map: follow the clues and
eventually there could be a big reward. At least that’s the hope from a
new study published in the journal Nature that discovered a novel
protein called ceramide-1 phosphate transport protein — a finding that
could eventually lead to the development of new drugs to treat a variety
of cancers and other conditions involving inflammation and thrombosis,
or blood clotting.
The identification of CPTP was the
result of an international collaboration that built on prior research by
co-lead author Charles Chalfant, Ph.D., Endowed Chair of Cancer Cell
Signaling and member of the Cancer Cell Signaling program at Virginia
Commonwealth University Massey Cancer Center as well as professor in the
Department of Biochemistry and Molecular Biology at VCU School of
Medicine. The team discovered that CPTP regulates levels of biologically
active lipids, which are molecules such as fatty acids that often play a
role in cell signaling. As its name implies, this study determined that
CPTP’s main function is to transport ceramide-1-phosphate, 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 shines a light on the cellular
mechanisms that contribute to these diseases.
“We may have identified the newest
target for treating cancer,” says Chalfant. “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.”
With assistance from Massey’s Lipidomics
Developing Shared Resource core, the researchers were able to determine
the composition of the bioactive lipids regulated by CPTP. Residing in
the cytosol, or the liquid within cells, the team 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 synthesise eicosanoids from
fatty acids in the membrane.
Confirming a decade of research from
Chalfant’s laboratory, 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,” says Chalfant. “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.”
Source: Science Daily.
0 Comments