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Mutation in gene allows cancer to spread: research

A group of scientists sponsored by the National Science Council (NSC) yesterday publicized the results of their research into how tumor cells migrate from one part of the body to another, a key complication that counters cancer treatment.

Project leader Yang Pan-chyr (楊泮池), dean of National Taiwan University’s College of Medicine and an Academia Sinica research fellow, and doctoral student Wang Shu-ping (王書品) told a press conference their research uncovered a pathway in which a gene that normally suppresses tumors instead allows the cancer to progress.

The breakthrough was published in the journal Nature Cell Biology this month.

“Lung cancer is involved in most cancer deaths in Taiwan and one of the reasons is that less than 30 percent of patients are diagnosed when their tumors are still operable, while the tumor cells migrate to other parts of the body in about 80 percent of patients,” Yang said.

About 7,000 cases of lung cancer are diagnosed each year in Taiwan, Yang said, adding that many of the patients are female non-smokers.

“There are many types of lung cancer and the prevalence of each is different for Caucasians and Asians, so it would be wrong to think that we do not need to conduct our own research,” he said.

As such, Yang’s team decided to focus their research on “p53,” a known tumor-suppressing gene that can restrict the progression of cancer by inhibiting proliferation and killing tumor cells, Yang said.

“While p53 is an important tumor suppressor, it is very prone to mutation [caused by ultraviolet rays, radiation or other carcinogens] and the mutated p53 is often associated with tumor growth,” Wang said.

The research project involved 79 patients with what is called non-small-cell lung cancer, 46 of whom had the normal p53 gene and 33 of whom had the mutated p53 gene.

The researchers found that the normal p53 gene promoted expression of MDM2, a lower-level protein.

“Another important discovery we made was that after the normal p53 promotes MDM2 expression, p53 and MDM2 bind with ‘Slug,’ which is a cancer cell invasion promoter,” Wang said.

When alone, Slug represses a transmembrane protein called E-cadherin that helps the body fight cancer. But when locked into a p53-MDM2-Slug combination, its danger is minimized.

Slug is harmful because it represses a transmembrane protein that adheres cells with cells, allowing them to form a tight structure that is resistant to cancer invasion, Wang said.

If a patient carries the mutated p53, however, the p53-MDM2-Slug combination is not formed and Slug is free to repress E-cadherin, increasing the risk of cancer invasion, he said.

“Having found the p53-MDM2-Slug pathway, our next step will be to develop cancer treatment drugs. Some drug candidates that repress Slug expression are already underway,” Yang said.

In addition, blood tests may be developed to test whether a patient’s p53 is normal or has mutated, Wang said.
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