Researchers at the University of California, San Diego School of Medicine have come across a new protein pathway which could be a precursor for the initiation and progression of colorectal cancer while aiding to predict survival rates in these cancer patients. This study was published in the online issue of eLife journal.
The protein known as Dishevelled-associating protein, or Daple, is found abundantly within the human body, secreted by almost all healthy cells. The main focus of the study lies within the fact that this protein is also tumour suppressor in the early stages of the disease but can also support the progression of cancer once malignant cells have started to circulate in the bloodstream after escaping their primary tumor location.
In this study, a total of 173 patients with stage 2 colorectal cancer and 51 patients with stage 4 of the disease were assessed. Their Daple levels were measured and compared using a combination of techniques including 3D tumour cell culture tests, fluorescent imaging studies and other advanced molecular techniques. Those in stage 2 of the disease and low levels of Daple showed worse outcomes over a two-year period, while higher levels of the protein were associated with better patient survival in the same period of time. Among patients diagnosed with stage 4 colorectal cancer, those with high Daple levels had an increased 20 percent survival over a 1,000-day period, compared with a 100 percent survival for patients with low levels of the protein. Over a three-year period it was observed that patients with lower Daple levels had a higher survival rate (close to 75%) whereas there were hardly any survivors with high levels of the protein.
The main mechanism behind Daple protein function lays within its ability to regulate the activity of a family of cell-signaling proteins, known as G proteins. These family of proteins help cells to sense and respond to different phenomena surrounding their microenvironment. Importantly, about 30 percent of all prescription drugs affect cells via G-protein-coupled receptors.
Dr. Pradipta Ghosh, MD, an associate professor of medicine, and the study’s senior author, commented ”Daple is a double-edged sword. The protein is a tumor suppressor early on but heralds faster death in advanced stages of colorectal cancer. We are working to figure out why. Our next challenge is to figure out how we can exploit Daple’s beneficial attributes while inhibiting its negative ones”.