Cancer Stem Cells Addicted to Methionine, Study Shows

Singapore researchers have discovered that cancer stem cells consume the amino acid methionine much faster than it can be generated, and this vulnerability could be exploited for cancer treatment.

AsianScientist (Jun. 10, 2019) – A research group in Singapore has discovered that cancer stem cells have unique nutrient requirements, with implications for tumor formation and treatment. Their findings are published in Nature Medicine.

The number of cancer cases has been increasing over the years, and one in every four to five people in Singapore may develop cancer in their lifetime. While there are many treatments for cancer, some patients’ tumors may be resistant to therapy, or relapse after a few years. This is thought to be due to the presence of cancer stem cells, which have a different metabolism from normal cells of the body.

In the present study, researchers led by Dr. Tam Wai Leong at the Genome Institute of Singapore (GIS) used advanced genomics and metabolomics technologies to accurately pinpoint the unique nutritional requirements of cancer stem cells. They showed that cancer stem cells consume methionine—an essential amino acid—at a rate that far outstrips its regeneration, which means that the cancer stem cells become addicted to the amino acid.

They also demonstrated that S-adenosylmethionine (SAM), a derivative of methionine, is involved in the regulation of critical gene functions in cancer stem cells. Importantly, the team noted that a metabolic enzyme known as methionine adenoyltransferase 2A (MAT2A) is responsible for converting methionine to SAM.

“MAT2A is an interesting enzyme that controls the metabolism of cancer cells. From our findings, this enzyme represents an important new drug target, as its inhibition led to the ablation of cancer stem cells. This paves the way for the development of next-generation drugs that target this dependence on methionine,” said Dr. Wang Zhenxun of GIS, the first author of the study.

The article can be found at: Wang et al. (2019) Methionine Is a Metabolic Dependency of Tumor-initiating Cells.


Source: A*STAR; Photo: Luis Molina/iStock.
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