Cancer cells use a mutant gene to coerce neighboring healthy tissue into helping with the disease's growth and spread, a major new study reports.
Healthy cells are persuaded to release unique growth signals which cancer cells can use to multiply but cannot secrete themselves, researchers found. Their study sheds light on how cancer cells and normal cells communicate with each other, and could open up new approaches to cancer treatment.
Scientists found that faulty versions of the KRAS gene - often mutated in cancer - can have an important effect on healthy tissue.Normal KRAS makes occasional signals that tell a cell to divide, but when mutated the gene becomes hyperactive and helps drive cancer cells' rapid and uncontrolled growth.
In the new study, researchers found that mutated KRAS also plays an important role in turning healthy 'stromal cells' into cancer's allies. The study showed for the first time that there is a communication loop with a cancer-causing gene controlling cancer via healthy stromal cells.
The researchers studied communication networks in cells from a type of pancreatic cancer called pancreatic ductal adenocarcinoma - one of the most deadly forms of cancer responsible for around 9,000 deaths each year in the UK. KRAS is mutated in more than 90 per cent of pancreatic cancer, and in nearly 20 per cent of all cancers.
The team studied thousands of different growth factors, proteins, and receptors across different pancreatic ductal adenocarcinoma cells to see how signals were being transmitted. They recognised well known pathways that KRAS uses to communicate with neighboring healthy cells but also noticed something unusual.
By monitoring proteins in the two cells at the same time, they discovered that healthy cells were responding with a totally new message - a message that doubled the capacity for KRAS to drive malignant behavior in the cancer cells.
They found that KRAS establishes a reciprocal signaling axis via heterotypic stromal cells. Reciprocal signaling further regulates tumor cell signaling downstream of KRAS and tumor cell behavior via AXL/IGF1R-AKT.
These results demonstrate that oncogene signaling should be viewed as a heterocellular process and that our existing cell-autonomous perspective underrepresents the extent of oncogene signaling in cancer.
Cancer cells turn healthy cells to the 'dark side'
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