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Early stage colon cancer characterized by inactivation of gatekeeper gene

The absence or inactivation of the RUNX3 gatekeeper gene paves the way for the growth and development of colon cancer, Singapore scientists report in the Sept. issue of the journal Cancer Cell. Previous studies have shown that RUNX3 plays a role in gastric, breast, lung and bladder cancers.

The inactivation of RUNX3 occurs at a very early stage of colon cancer, according to the Singapore scientists' studies with human tissue samples and animal models.

Because the inactivation of RUNX3 is relatively easy to detect, and it is possible that inactivated RUNX3 can be reactivated, this new research may prove to be a crucial step in the development of an early diagnostic test as well as a therapeutic target for colon cancer.

Prior to these new findings, scientists knew that a tumor suppressor gene called APC is disrupted in most cases of human colon cancer. APC disruption activates bete-catenin and TCF4, a protein complex that plays an important role in cancer development. For decades, this has been considered the molecular basis for colon cancer.

These latest findings are the first to show that the activity of beta- catenin/TCF4 also is inhibited by RUNX3.

The Singapore scientists are based at the National University of Singapore's (NUS) Yong Loo Lin School of Medicine and the Institute of Molecular and Cell Biology (IMCB), one of the 14 research institutes under the country's Agency for Science, Technology and Research (A*STAR).

In an earlier research, the same team of researchers reported that RUNX3 is a major tumor suppressor of gastric cancer.

Leading the Singapore team is Yoshiaki Ito, M.D., NUS Yong Loo Lin Professor in Medical Oncology and a principal investigator at IMCB.

In their latest study, supported by A*STAR, Dr. Ito and his team analyzed animal models as well as tissue samples from patients diagnosed with colon cancer, with prior ethical approval obtained from the Institutional Review Board, to examine how RUNX3 is involved in colon cancer.

"My team and I have been working on our research for the past six years, and we are extremely excited about how our research findings can be translated into practical clinical applications to help patients suffering from cancers such as bladder, breast, colon and lung," said Dr. Ito. "We certainly look forward to our continuous teamwork with our clinical colleagues in improving the lives of cancer patients,"

The body usually has a fail-safe mechanism to get rid of abnormal cells. However, this does not work when RUNX3 is not present. RUNX3 is a gene that acts as a gatekeeper and prevents the uncontrolled growth of cells that may result in cancerous tumor. Disruption of the RUNX3 gene can cause colon cancer as well as many other types of cancers, including those of the bladder, breast, colon and lung.

Said John Wong, M.D., who is Dean of the Yong Loo Lin School of Medicine and director of Singapore's National University Cancer Institute, "Professor Ito's research offers exciting, fresh hope as it lays the groundwork for a diagnostic kit for early detection of colon cancer as well as a possible therapeutic target."

Lee Eng Hin, M.D., Executive Director of A*STAR's Biomedical Research Council, said, "This is a wonderful example of world-class research being done here. As biomedical research efforts in Singapore begin to reap clinically significant outcomes, the working relationships between our scientists and hospital clinicians must be further strengthened. Not only does the success of Professor Ito's work open new doors to colon cancer treatment, it also serves as a leading example for other scientists to follow."


Contact: Cathy Yarbrough
Agency for Science, Technology and Research (A*STAR), Singapore

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