Tumour cells have the ability to continue surviving when glucose levels are very low. This could be one of the reasons why widely-used anti-angiogenic agents often fail to eliminate cancer. A group of CNIO researchers have identified one of the key biochemical mechanisms that allow cancer cells to survive without glucose.
In particular, they have discovered a group of proteins that actually act as a switch: when food -glucose- is available, tumour cells use a particular biochemical path to survive and continue to proliferate; when there is no glucose, the switch triggers a different path to achieve the same goal, namely the survival of the tumour cells.
‘Three proteins: URI protein - which act as the switch, OGT and c-Myc a well known oncogene, and a protein needed for cancer cell survival upon nutrient stress.’
As explained by Nabil Djouder, researcher at the CNIO and the intellectual author of the paper published in Cancer Cell, "tumour cells are very smart; when one door that seemed essential for their growth and proliferation closes, they open new ones that allow them to adapt to any stress and survive. This is why they develop highly sophisticated mechanisms and learn to survive, and this is why it is so difficult to cure cancer".
Djouder and his partners have identified the system of switches that allows cells to detect whether or not there is glucose, and to decide, in the light of this, what biochemical path they must follow to achieve their ultimate goal, which is to survive.
This is a sophisticated system composed with three proteins: URI protein (which act as the switch), OGT and c-Myc. c-Myc is a well known oncogene, i.e. it promotes cell proliferation and survival. However, Djouder's group has discovered that c-Myc protein levels matter for cancer cell survival upon nutrient stress.
Our findings suggest an important glucose-sensing mechanism in which URI acts as a rheostat controlling OGT activity and therefore c-MYC levels, conferring selective traits that allow cancer cells to tolerate severe metabolic stress and survive under selective pressures imposed by environmental challenges".
This mechanism can be of general importance in tumorigenesis and may explain how cancer cells exposed to glucose deficiency can expand instead of regressing".