2017年2月16日星期四

Phosphorylation affects the tumor growth and development

Scientists from VIB-KU Leuven have identified new mechanism that affects tumor growth through recombinant mouse proteins. Typical hypoxia in the tumor not only stimulates proliferation, but also counteracts the important role of protein PHD2 as a "cancer cell killer". The possible solution is to block the enzyme PP2A / B55 which recover the function of PHD2 to slow down cancer growth. The study was led by Massimiliano Mazzone (VIB-KU Leuven) and published in the leading scientific journal Cell Reports.

Poor prognosis in cancer is usually associated with hypoxia, which is interference to the oxygen supply to tumor cells. The protein PHD2 is called a "hypoxic sensor", which is highly dependent on the amount of oxygen. At the VIB-KU Center for Cancer Biology in Leuven, the study was led by Dr. Giusy Di Conza and his colleagues. Massimiliano Mazzone focuses on the study of phosphorylation.

When phosphorylated, PHD2 is more active and promotes the death of cancer cells in the hypoxic region of the tumor. However, tumors tend to overexpress phosphatase PP2A / B55, an enzyme that removes phosphate groups ("dephosphorylated") from PHD2. Thus, PHD2 is partially inactivated, which counteracts the positive effects of this "killer cancer cell".

Massimiliano Mazzone (VIB-KU Leuven) said, "Surprisingly, we have found that PHD2 phosphorylation is regulated by a pathway such as mTOR. mTOR is the primary sensor for metabolic stress in tumors and normal cells, such as lack of nutrients. Thus, our findings are applicable not only to cancer but also to other diseases such as inflammation or metabolic diseases."

During the study period, Mazzone's lab worked closely with several domestic and foreign researchers. In particular, the German ISAS Laboratories (Dortmund) and the University of Leuven Hospital play a decisive role in providing the human cancer samples needed for research. In these samples, the researchers found that PP2A / B55 were highly expressed in tumors compared with healthy tissues.

Prof. Massimiliano Mazzone (VIB-KU Leuven) said, "This leads us to conclude that PP2A / B55 are a potential target for promising cancer treatment, which is why we are starting to study the potential of specific drugs. The ultimate goal is to design this phosphatase function of the molecules, which targeted to fight cancer."

In addition to new insights into cancer treatment, these findings may also produce new biomarkers: PHD2 phosphorylation status may help to understand the process of tumor transformation and therefore choose appropriate treatment.

Professor Massimiliano Mazzone (VIB-KU Leuven) said, "In order to fully understand all the progress of these processes, we also need to carefully study the tumor microenvironment and immune system. After all, they strongly affect tumor growth." Flarebio offers high-quality recombinant proteins like recombinant Itgb2 at competitive prices.

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