High energy stores of glycogen found in cancer cells may be contributing to the aggressive spread of breast cancer.
More than fifty percent of solid tumours have regions of hypoxia (i.e., areas receiving inadequate levels of oxygen), which have been associated with metastasis (the spread of cancer) and poorer outcomes in many types of cancers, including breast cancer. Research has found that a hypoxic environment is linked to the spread of breast cancer and patient death. When cells are deprived of oxygen, they respond by activating particular cell signaling pathways. One such response to a hypoxic environment is the build-up of glycogen, a main energy-storing molecule. This glycogen can then be used as an energy source to aid the spread of breast cancer. In many cancers, high levels of glycogen have been found in the cancer cells and in the cores of the hypoxic tumours.
In a recent study published in PLOS ONE, researchers from the United States studied the link between glycogen stores in cancer and their ability to influence its invasion and spread throughout the body. The team first measured the amount of glycogen stores present in cancer cells of several different breast cancer types. Depending on oxygen levels, they discovered that breast cancer cells are capable of storing large amounts of energy, nearly as much as the liver – the key organ responsible for storing glycogen. This means cancer cells could break down and convert the glycogen into needed energy for its growth and spread through the body.
Next, the team studied how glycogen energy stores and its metabolism are affected after a protein enzyme (PYG) responsible for glucose metabolism is inactivated. The loss of this key enzyme resulted in a decrease in the cancer cells’ ability to break down and convert the glycogen into energy, thus decreasing the cancer’s ability to proliferate and spread. The inability of the cancer cells to use their glycogen stores meant that the cancer was much less aggressive. This key finding should prompt and guide future research on glucose metabolism in not only breast cancer but other cancers as well.
The team hopes that these findings can help in the discovery of a potential new treatment targeted at the PYG enzyme to treat or prevent the spread of breast cancer and will be explored in further animal studies.
Written by Maggie Leung, PharmD.
Altemus, M. A., Goo, L. E., Little, A. C., Yates, J. A., Cheriyan, H. G., Wu, Z. F., & Merajver, S. D. (2019). Breast cancers utilize hypoxic glycogen stores via PYGB, the brain isoform of glycogen phosphorylase, to promote metastatic phenotypes. Plos One, 14(9). doi: 10.1371/journal.pone.0220973
Study: Aggressive breast cancers store large amounts of energy, which enables it to spread. (2019, October 4). Retrieved from https://www.eurekalert.org/pub_releases/2019-10/mm-u-sab100419.php.
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