The balance of two enzymes is related to pancreatic cancer survival

The pancreas is deep in our upper abdomen, which is an inconspicuous organ. Although it is small, it is very important to human. The pancreas produces digestive enzymes that help digest foods especially fats, and it also makes hormones that maintain blood sugar balance.

The pancreas is comprised of abundant cells. Normally, cells in our body update every day. Cells divide to form new cells to meet the body's needs. It means that old cells die, newly produced cells will replace them. When new cells are too many to body properly use them, they will accumulate together to form a mass, which is called cancer-pancreatic cancer.

Pancreatic cancer is one of the malignant cancers. Once it is diagnosed, it is already in the middle or late stage. It is very difficult to treat and its prognosis is poor. Thousands of people die due to the disease in the world per day. It is one of the global health concerns that attract widespread attention in the medical community.

A recent study, published in the Molecular Cell, has shown a protein called PHLPP1 that negatively regulates the protein kinase C (PKC) enzyme content. This study lays the foundation for the future use of PHLPP1/PKC levels in patients with pancreatic cancer as a predictor of prognosis and provides hope for the development of new therapeutic drugs that inhibit PHLPP1 and promote PKC.

Researchers at the University of California, San Diego School of Medicine found that high-PHLPP1 levels in pancreatic cancer result in low PKC levels, which is associated with low patient survival.

In the past few decades, PKC has been considered to promote tumors, and many researchers have also tried to develop drugs that inhibit PKC as a method of controlling cancer. However, their research suggested that, conversely, anticancer drugs actually increase PKC activity. Because protein kinase C (PKC) enzymes are critical for many cellular activities, including cell survival, proliferation, and migration-functions that must be carefully controlled to prevent cell loss and tumor formation.

By revealing how cells regulate PKC activity, the researchers discovered that as long as the cells are overexpressed PKC, the PHLPP1 proofer will mark it as destroyed. This means that the amount of PHLPP1 in the cell determines the PKC content.

The researchers then collaborated with Dr. Gordon Mills of the OHSU Knight Cancer Institute to analyze the tumor protein database, which also included patient information related to each tumor. Among the 105 pancreatic tumors included in the database, those with high levels of the correcting enzyme PHLPP1 had low levels of PKC.

More importantly, the high PHLPP1/low PKC ratio was associated with poor prognosis. Pancreatic patients without a low PKC in the database survived for more than five and a half years. On the other hand, half of the patients with low PHLPP1/high PKC survived longer.

Based on a comprehensive analysis of the findings, the researchers believed that if pancreatic cancer patients can be detected with high PHLPP1 and low PKC, the doctors know that the prognosis is not good. At this point, we can suppress their PHLPP1, resume PKC activities and ultimately improve their chances of survival.

Although it is still in the early stages, researchers hoped that this information may one day contribute to the diagnosis and treatment of the pancreas.

Now they plan to screen compounds that inhibit PHLPP1 and restore PKC levels in low PKC pancreatic cancer cells in the laboratory. These may become the basis of a new treatment for pancreatic cancer.

Cite this article

CUSABIO team. The balance of two enzymes is related to pancreatic cancer survival.


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