Research

“Missing link” discovered in tumour suppression mechanism by Prof Yoshiaki Ito and team

Investigators from the Cancer Science Institute of Singapore (CSI Singapore) at NUS and Chungbuk National University in Korea have found that RUNX3, a gene much studied for its role as a tumour suppressor, could be a key player in preventing early tumour formation.
Headed by Professor Yoshiaki Ito of CSI Singapore and Professor Suk-Chul Bae in Korea, the team’s research on lung cancer uncovered that RUNX3 is an important component in a tumour suppression mechanism which involves p53, a tumour suppressor protein regulating cell proliferation and preventing cancer. The findings reported in top scientific journal Cancer Cell on 11 November 2013 provide the basic understanding that helps explain the development of other types of human cancers.

Half of almost all cancer types show p53 gene mutation, suggesting that the gene’s inactivation contributes to cancer development. However, even though the gene kills well-developed cancer cells, it has little effect in preventing the initial stages of cancer formation.
The research thus uncovered the “missing link” of the tumour suppressor pathway that regulates p53 function, and provides knowledge for deeper insights into the complex mechanisms regulating gene expression and associated cancer development when disruption happens.

This breakthrough discovery has potential applications in early cancer detection and prevention, said Prof Ito. Cancer-specific epigenetic inactivation of RUNX3 features DNA methylation, a chemical process that “switches off” the gene without changing its coding information. The DNA methylation can be readily screened for early detection or prognosis of a wide variety of cancer. This also has encouraging implications that if RUNX3 inactivation is reversed by drugs or other approaches, cancer growth may be retarded, he said.

Prof Ito explained: “It is very likely that our body is protected by two lines of defence mechanisms against lung cancer development – RUNX3 forms the first line which protects against adenoma formation while p53 forms the second line in protecting against adenocarcinoma formation. It will be important to examine whether other types of cancer also show two lines of defence mechanisms, since p53 is frequently inactivated in various cancer types.”

He noted that “clinical trials have shown that reactivation of epigenetically inactivated genes is feasible” and RUNX3 gene can be made active again by chemicals in cancer cells. The team’s next step is to find a way to effectively re-ignite RUNX3 activity during the early phases of cancer to arrest cancer development before permanent abnormal changes occur.

Source: NUS News