Cancer can be the end result of a wide range of things that go wrong, and understanding how is key to prevention and treatment. Now, scientists have discovered a cancer-causing mechanism that has never been seen before – a kind of clog in a cellular garbage disposal system.
The breakthrough began when Harvard Medical School researcher Megan Insco identified a tumor-suppressing gene called CDK13 while studying zebrafish. Mutations in this gene were found to speed up the development of melanoma. When checked against human melanoma, CDK13 was found to be mutated in many cases.
On closer inspection into CDK13’s function, Insco found that the protein is involved in a cellular cleanup system. It regulates a series of other proteins that ensures defective RNAs made in the cell are removed in a timely manner, but mutations interfere with that vital cleanup.
“There are hundreds of steps in making RNAs, and sometimes it doesn’t go right,” said Insco. “They’re mistakes that are usually discarded. In this case, we found that the cell was not cleaning them up. The vacuum cleaner was broken, so the RNAs were building up.”
Sure enough, when Insco tested the effect of these leftover RNA molecules on melanoma, she found that they drastically accelerated the progression of the cancer. The team checked a series of human cancers for mutations in CDK13 or the proteins it regulates, and found that 21% of the melanoma tumors they checked had such mutations. Similar mutations were also found in cancers of the lung, uterus, colon, and non-melanoma skin cancers.
Identifying the problem is an important step, but it’s just the first. Now begins the research into how to target this mechanism to uncover new potential treatments. The team’s next step is to investigate whether the cancer-promotion is caused by the damaged RNA molecules themselves or if they’re producing abnormal proteins.
The research was published in the journal Science.
Source: Harvard Medical School
