KAIST's Kim Se-youn, Korea University's Byun Young-joo lead joint study finding metabolite 13-HODE blocks mTOR protein
The protein mTOR becomes excessively active in cancer cells, driving tumor growth and metastasis. The molecular mechanisms that precisely regulate mTOR activity, however, have remained poorly understood.
KAIST announced Monday that a research team led by professor Kim Se-youn of its Department of Biological Sciences, working jointly with a team led by professor Byun Young-joo of Korea University's College of Pharmacy, has discovered that 13-HODE — a lipid metabolite produced when fatty acids are broken down in the body — suppresses the activity of mTOR, a key regulator of cancer cell growth.
The findings open a potential pathway for developing next-generation anticancer treatment strategies.
The research teams focused on substances capable of binding to the mTOR protein, particularly naturally occurring metabolites the body produces on its own. Through large-scale metabolite screening — a technique that analyzes vast numbers of biological metabolites — they identified 13-HODE, a lipid metabolite generated as fats are processed in the body. The compound binds directly to the active site of mTOR, halting its function in cancer cells.
13-HODE is produced in the body during the metabolism of linoleic acid, an essential polyunsaturated fatty acid found abundantly in vegetable oils. In that process, the enzyme ALOX15, which drives fatty acid oxidation, oxidizes linoleic acid to generate 13-HODE.
The teams demonstrated that increasing the production of ALOX15 and 13-HODE reduces mTOR activity and suppresses cancer cell growth.
The central finding of the study is that 13-HODE does more than simply inhibit cancer cell growth. The researchers identified the molecular mechanism by which it directly binds to mTOR — the protein central to cancer progression — and blocks its activity.
"We believe this research can serve as foundational technology for developing metabolism-based treatment strategies that suppress cancer cell growth," Kim said. "Going forward, this concept may also be applicable to a range of diseases in which mTOR signaling is overactivated, such as inflammation and aging."
The study was selected as the cover article of the May issue of Cell Chemical Biology, an international journal in the field of chemical biology.
nbgkoo@heraldcorp.com
