Researchers at the Salk Institute in collaboration with researchers from the University of Basel in Switzerland have discovered a protein called LHPP, which acts as a molecular switch to turn off the uncontrolled growth of cells in liver cancer. Tumor suppressor that can be used as a biomarker to diagnose and monitor treatment of liver cancer, may also be used in other types of cancer. The work is published in Nature March 29, 2018.
"I think we have discovered a new cellular proteins control mechanism, which is in violation can cause cancer - says Professor Tony Hunter, the author of the article -. It gives new possibilities for therapy and diagnosis of cancer."
Hunter is known that in 1979 he discovered the molecular signaling process called tyrosine phosphorylation. In this process, proteins called kinases attach phosphate to the chemical tyrosine amino acids in target proteins. When violations tyrosine phosphorylation leads to uncontrolled cell growth and cancer. Hunter's work has helped to develop a new class of anti-cancer pharmaceutical drugs called tyrosine kinase inhibitors, including the important leukemic drug Gleevec.
Since Hunter Lab continues to study the phosphorylation process not only in terms of the addition of phosphate, but also to their removal. In 2015 godu antibody has been developed for the identification and study of phosphate associated with a different amino acid, called histidine.
In the new work an international team of scientists led by Professor Michael Hal University of Basel studied mouse models of the most common form of primary liver cancer - hepatocellular carcinoma. In order to compare the tumor cells to normal, the team analyzed more than 4,000 proteins in healthy and diseased liver. By the end of the three proteins were identified: histidine kinase NME1 and NME2 in tumor cells has been increased, and the level of histidine phosphatase LHPP was insufficient.
This gave the researchers the key to the study of phosphorylation of histidine as a potential target. They found that the protein levels of phosphorylated histidine were significantly higher in tumor tissue than in normal liver tissue.
NME1 NME2 and histidine kinases are known, and LHPP - gistidinfosfatazoy. In further experiments, the team confirmed that LHPP is a tumor suppressor, "off" switch for the treatment of cancer. Repeated administration of the protein in the liver of mice prevented the formation of tumors.
When the researchers examined samples of human liver tumors, they found a similar picture: NME1 levels were high and NME2 and LHPP - low compared to healthy tissue. In addition, the base obtained from various human cancers data on cancer genome showed that a significant proportion of human liver cancer is low LHPP, and disease severity and longevity correlated with its levels.