Researchers have identified a mechanism that allows cancer cells to respond and grow rapidly when levels of sugar in the blood rise, according to a news release. The finding may help to explain why people who develop conditions in which they have chronically high sugar levels in their blood, such as obesity, also have an increased risk of developing certain types of cancer.
The findings were published Nov. 17 in the journal eLife, by Susumu Hirabayashi, who leads the Metabolism and Cell Growth group at the MRC Clinical Sciences Centre at Imperial College London, and Ross Cagan of the Icahn School of Medicine at Mount Sinai, in New York.
The study was conducted on the fruit flies Drosophila melanogaster, but used flies genetically engineered to activate the Ras and Src genes that are activated in a variety of cancers in humans. They found tumor cells detect glucose availability through a protein called salt-inducible kinase.
“Our results suggest that if we can develop drugs to target SIK and stop it from alerting cancer cells in this way, then we may be able to stop cancer cells from thriving in an insulin-resistant environment and break the connection between obesity and cancer,” Hirabayash said in the release.
Before scientists can develop drugs to block SIK, they must first confirm that a similar mechanism happens in people.
Building on past research
The researchers built on a study Hirabayashi published two years ago using fruit flies with Ras and Src activated. When the flies were fed a high sugar diet, normal cells became insulin resistant but tumor cells actually became more sensitive to insulin. They turned on a metabolic switch that triggered them to produce extra receptors for insulin, but how that switch was turned remained unexplained.
In the new study, Hirabayashi and Cagan found the tumor cells detect glucose availability indirectly, through SIK. When glucose levels are high, SIK sends a signal along a route called the Hippo signalling pathway.
The Hippo signalling pathway is known to play a role in controlling cell growth. When it’s turned on it keeps cell growth under control, but if it is turned off, the cell can carry on growing, and may ultimately develop into a tumor. Hirabayashi and Cagan found SIK acts like a sugar sensor, turning the Hippo signaling pathway off, in response to raised glucose levels. This allows the tumour cells to continue to grow. “Ras and Src co-activated tumors use SIK to sense that there’s lots of glucose available outside of their cells, and to tell the cells to take advantage of that,” Hirabayashi said in the release.
These tumors are extremely sensitive and poised to respond quickly to changes in the Hippo signaling pathway. “Together, Ras and Src co-activated tumours use SIK to efficiently respond to glucose availability and ensure the tumours grow in nutrient rich condition such as obesity,” Hirabayashi said in the release. “We still don’t know if tumors caused by other genes respond to sugar in the same way.”
Conditions such as obesity and cancer are too often studied in isolation, Hirabayashi, said in the release. “If researchers from these two fields of expertise were to work more closely together, each might gain useful insights from the other about possible connections.”
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