KAIST identifies natural 'brake' that suppresses cancer cell growth

The mTOR protein becomes excessively active in cancer cells, driving tumor growth and metastasis. The molecular mechanisms by which mTOR activity is precisely regulated have remained poorly understood.

KAIST announced Monday that a research team led by professor Kim Se-yun of its Department of Biological Sciences, in collaboration with 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 team focused on substances capable of binding to the mTOR protein, particularly naturally occurring metabolites the body produces itself. Through large-scale metabolite screening — a technique that analyzes vast numbers of biological metabolites — the team found that 13-HODE, a lipid metabolite generated as fats are processed in the body, directly binds to the active site of mTOR and halts its function in cancer cells.

The 13-HODE molecule is produced during the metabolism of linoleic acid, an essential polyunsaturated fatty acid abundant in vegetable oils. In that process, the enzyme ALOX15, which drives fatty acid oxidation, converts linoleic acid into 13-HODE.

The study's central contribution goes beyond establishing that 13-HODE has cancer-suppressing properties. The team mapped the precise molecular mechanism by which 13-HODE physically binds to the mTOR protein and blocks its function at the source.

The researchers demonstrated that increasing the production of ALOX15 and 13-HODE reduces mTOR activity and inhibits cancer cell growth.

Kim said the discovery could serve as foundational technology for developing metabolism-based treatment strategies that suppress cancer cell growth, adding that the concept may also apply to other conditions 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.