Cancer tumors manipulate a natural cell process of nonsense decay (NMD) to promote their survival suggesting that controlling this mechanism could stop progress of the disease, according to new research published in the journal Nature Communications.
NMD is a natural physiological process that provides cells with the ability to detect DNA errors called nonsense mutations. It also enables these cells to eliminate the mutated message (decay) that comes from these faulty genes, before they can be translated into proteins that can cause disease formation. NMD is known among the medical community for the role it plays in the development of genetic diseases such as Cystic Fibrosis and some hereditary forms of cancers. But not all nonsense mutations can elicit NMD, so until now, it's wider impact on cancer was largely unknown.
Researchers developed a computer algorithm to mine DNA sequences from cancer to accurately predict whether or not an NMD would eliminate genes that had nonsense mutations. The work originally focused on ovarian cancers, and found that about a fifth of these cancers use NMD, to become stronger. This is because NMD ensures that the message from a gene called TP53, which ordinarily protects cells from developing cancer is almost completely eliminated. In the absence of NMD, a mutated TP53 might still retain some activity but NMD ensures that this is not the case.
Based on this research, the team predicts that because cancers essentially feed on NMD, they become dependent on it in some cases. If scientists were therefore able to inhibit or control the process, it is possible that they could also control cancer and prevent the progression of the disease.
Co-author said: 'Our first observations of evidence of the role of NMD in ovarian cancer were tantalizing. We found that NMD precisely explained why there was almost no expression of TP53 in certain ovarian cancers. We went on to test the role of NMD in other cancer types and the evidence of the role of NMD was compelling. This opens the door for exciting possibilities for customized treatments including individualized immunotherapies for patients in the future.'
Following the ovarian cancer analysis, the team expanded the study to include other cancer types. They analyzed about a million different cell mutations in more than 7,000 tumors from the Cancer Genome Atlas covering 24 types of cancer. The team was able to map how each cancer type used NMD revealing the remarkable extent to which NMD helps cancer to survive.
Moving forward the team will focus on testing their theory and understanding to what degree stopping the NMD process allows them to control tumors.
Tumors depend on nonsense decay (NMD) process for survival!
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