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Scientists at VIB-KU Leuven have identified a new mechanism that impacts tumor growth. The typical lack of oxygen in tumors doesn't only stimulate proliferation, but also offsets the important role of the protein PHD2 as 'cancer cell killer'. A possible solution lies in blocking the enzyme PP2A/B55, which restores the function of PHD2 and consequently slows down cancer growth.
Poor prognosis in cancer is typically correlated with hypoxia, a disturbance in the oxygen supply to the tumor cells. The protein PHD2 is known as a 'hypoxic sensor', as its function is highly dependent on the amount of oxygen.
When phosphorylated, PHD2 is more active, promoting the death of cancer cells in the low-oxygen areas of the tumor. However, tumors tend to overexpress the phosphatase PP2A/B55, an enzyme that removes the phosphate group ('dephosphorylation') from PHD2. As a result, PHD2 is partially inactivated, which offsets the positive effects of this 'cancer cell killer'.
Prof. Massimiliano Mazzone (VIB-KU Leuven): "Surprisingly, we found that the phosphorylation status of PHD2 is regulated by pathways such as mTOR, which in tumor and normal cells represents the main sensor of metabolic stresses such as lack of nutrients or growth factors.
"This leads us to the conclusion that PP2A/B55 is a promising potential target for cancer therapy. That is why we started working together with an interested partner to study the potential of specific drugs against PP2A/B55. The ultimate goal is to design molecules that block the function of this phosphatase, thereby fighting cancer in a targeted way."
originally posted by: AnnaBecker
I read this totally different than you do. As I understand it low oxygen proliferates cancer cells. This is consistent with much of the other research I have done that points to cancer not being able to survive in an oxygen rich environment. "typical lack of oxygen in tumors doesn't only stimulate proliferation," and "Poor prognosis in cancer is typically correlated with hypoxia, a disturbance in the oxygen supply to the tumor cells." These statements tell me that lack of oxygen (like abundance of sugar) feeds cancer. What am I missing?