Oxygen is important for all living cells and it is used in the process of generating energy, in the form of a molecule called ATP, which is required to keep cells alive and working.
As tumours grow rapidly, they can start to outgrow the supply of oxygen, a term called hypoxia, and so in order to survive cancer cells have to adapt to new ways of making ATP without oxygen.
One very important molecule, called HIF, is central in allowing cancer cells to reprogram cellular metabolism to maintain sufficient energy (ATP) levels in the absence of oxygen. When oxygen is low, HIF can compensate by increasing the amount of glucose a cancer cell uses in order to maintain energy (ATP) production.
Reducing breast cancer cell survival
When cells increase the amount of glucose they use, they also increase a by-product called lactate which can make the cellular environment more acidic which can be damaging to cancer cells. Therefore, at the same time as increasing the use of glucose, HIF also turns on another protein called CAIX which helps maintain a neutral pH within the cancer cells helping them survive.
Therapeutic targets against breast cancer
In this work we have shown that in order for HIF to turn on CAIX at the same time as increasing the use of glucose, it requires another protein in the cell called CtBP. CtBP can detect how much glucose a cell is using and use this information to then turn on CAIX when the cancer cell starts using more glucose in response to low amounts of oxygen. We have shown that stopping CtBP from working prevents HIF from turning on CAIX, and this reduces breast cancer cell survival. Along with previous work, this further highlights CtBPs as potential therapeutic targets against breast cancer.
Glycolysis, via NADH-dependent dimerisation of CtBPs, regulates hypoxia-induced expression of CAIX and stem-like breast cancer cell survival is published in FEBS Letters, 3 July 2020Read full article