mRNA cap methylation - a key player in cancer cell growth?

One of the most prevalent cancer-causing genes or “oncogenes” is called PI3KCA.  Damaging changes or “mutations” in this oncogene are found in many cancers including cancers of the breast, colon, brain, liver, stomach and lung.   Understanding how cancer-causing genes such as PIK3CA change the behaviour of our cells is key to developing new therapies for cancer patients. 

Researchers at the Centre for Gene Regulation and Expression, University of Dundee have discovered that PI3KCA oncogene changes how cells require their protein contents to be made.  Professor Victoria Cowling’s research group found that breast cancer cells which carry cancer-causing PI3KCA oncogenes are dependent on cells making protein by using a process called “mRNA cap methylation”. In their experiments, the Cowling group found that by inhibiting the process of mRNA cap methylation, they could selectively reduce the growth of cancer cells carrying the PI3KCA oncogene. Currently the Dundee Drug Discovery Unit is developing inhibitors of mRNA cap methylation with the aim of preventing tumour growth.

“These recent findings are important because they direct our efforts to selectively targeting cancers with these PIK3CA oncogenic mutations”, said Professor Cowling.  The research was performed by two former students in the Cowling lab, Shanade Dunn, now a senior scientist at the pharmaceutical company Astra Zeneca in Cambridge, and Olivia Lombardi, now a research scientist at the Ludwig Institute for Cancer Research in Oxford University. The research was also assisted by Radek Lukoszek.  The work is published today in the Royal Society Journal, Open Biology.