Scientists Discover Signal Pathway That Allows Cancer Cells to Survive Low-Oxygen Environments

Recent research is helping scientists understand how cancer cells in tumors manage to survive without oxygen. A study published in Nature Cell Biology explains how cancer cells utilize a special signal pathway. An enzyme called protein-tyrosine phosphatase 1B, or PTP1B, sends signals that shut down any non-essential chemical processes that use oxygen. This allows the cancer cells to live in low-oxygen environments, such as in tumors.

The researchers were originally looking for tumor-suppressing molecules when they found the enzyme PTP1B. They noticed that PTP1B function was needed for the growth of cancerous cells in some types of cancer. One common type of breast cancer, for example, couldn’t survive in hypoxic environments if the cancer cells lacked PTP1B. The researchers also noticed that in cells with PTP1B, most signal pathways that use oxygen were shut down. In cells without PTP1B, these pathways continued to operate as normal.

PTP1B sends signals that turn off non-essential chemical processes. The enzyme also activates a pathway that switches cellular respiration mechanisms. Instead of gaining energy from oxidative phosphorylation, a process that uses oxygen, the cells switch to using glycolysis exclusively. Glycolysis alone doesn’t produce as much energy as oxidative phosphorylation but it doesn’t require oxygen. This allows cancer cells to survive in environments with low oxygen, including tumors.

The scientists investigated further and found that PTP1B partially works by controlling a protein called RNF213. RNF213 prevents certain enzymes, known as α-KGDDs, from consuming oxygen. This stops many of the chemical pathways that normally use large amounts of oxygen.

This research could be used to work on possible cures for certain types of cancer, including breast cancer. If it’s possible to turn off the pathways that cells use to survive low-oxygen environments, we could potentially kill cancer cells in hypoxic environments. This knowledge could also be used to treat a rare condition called Moyamoya disease. The disease causes abnormal blood vessel growth in the brain, leading to seizures and other problems. Moyamoya disease is associated with RNF213 activity so understanding how the protein works could provide new insight into treating the disease.

REFERENCE

Benjamin G. Neel et al. PTP1B controls non-mitochondrial oxygen consumption by regulating RNF213 to promote tumour survival during hypoxia. Nature Cell Biology (2016).

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