Long ago in more primitive times, stress signaled imminent danger, so thrombin kicked in, causing blood to clot -- just in case that saber-tooth tiger got ahold of its victim. In the present day, blood is more susceptible to clotting in the bodies of those with cancer. Conversely, people with activated blood coagulation are more likely to develop cancer, which helps explain why anti-coagulants may help treat and prevent certain cancers. How blood-clotting and cancer were linked had been unclear, however -- until now.
Proteins that speed up and slow blood-clotting thrombin production determine how much thrombin cells can produce. Both types of proteins (speed up and slow) bind to the cellular works that make thrombin, which is normally kept at low levels. But when cells come under stress from inflammation, another protein (p38 MAPK) adds a chemical tag to those thrombin-slowing proteins, allowing the proteins that speed up production to take charge. Inflammation caused by cancer could lead to increased thrombin levels, which may explain why cancer patients are more susceptible to blood clots.
The discovery of how p38 MAPK influences thrombin production holds implications for cancer treatments, especially since drugs that inhibit p38 MAPK are already being tested in clinical studies, said Matthias Hentze, associate director of the European Molecular Biology Laboratory and co-director of Molecular Medicine Partnership Unit in Germany.