KAIST

< (Left) Professor Seyun Kim from KAIST, (Right) Professor Young-Joo Byun from Korea University > 

'mTOR', a protein in our body, becomes excessively activated in cancer cells, promoting cell growth and metastasis. Korean researchers have discovered for the first time in the world that '13-HODE'—a substance produced when fatty acids, which are abundant in vegetable oils, are metabolized in the body—binds directly to mTOR and acts as a 'natural brake' that suppresses cancer cell growth. This research presents the possibility of developing next-generation anticancer treatment strategies. Our university announced on the 2nd that a joint research team led by Professor Seyun Kim from the Department of Biological Sciences and Professor Young-Joo Byun from the College of Pharmacy at Korea University (President Dong-One Kim) has discovered that the lipid metabolite '13-HODE' (a lipid metabolite produced when fatty acids are metabolized) suppresses the activity of mTOR, a key regulatory factor in cancer cell growth. In addition, this research involved joint participation from Professor Mi Young Kim from the Department of Biological Sciences at KAIST, Professor Byung-Chul Oh from the College of Medicine at Gachon University (President Gil-ya Lee), and Professor Patrick L. Wintrode and Professor Daniel Deredge from the School of Pharmacy at the University of Maryland, USA. mTOR is an important enzyme (a protein that helps biological reactions) that regulates cell growth and energy usage. However, in cancer cells, mTOR activity is known to increase abnormally, promoting cell proliferation and metastasis. For this reason, anticancer research aimed at controlling mTOR is being actively conducted worldwide. The research team focused on substances capable of binding to the mTOR protein, particularly natural metabolites produced by the body itself. Through extensive metabolite screening (a technology that analyzes large quantities of metabolites in vivo), they discovered that a lipid metabolite called '13-HODE', which is formed as fat changes in the body, attaches directly to the active site of the mTOR protein and stops its operation in cancer cells.

< (AI Image) Cancer cell growth suppression effect based on direct inhibition of mTOR by linoleic acid-derived 13-HODE > 

The 13-HODE (13-Hydroxyoctadecadienoic acid) molecule is produced in our body during the process of metabolizing linoleic acid (an essential unsaturated fatty acid), which is abundant in vegetable oils. In this process, 'ALOX15 (an enzyme that induces a fatty acid oxidation reaction)' oxidizes linoleic acid to produce 13-HODE. The core of this research goes beyond the simple level of showing that 13-HODE has anticancer efficacy; it clarifies the molecular mechanism (the biological principle of operation) by which 13-HODE physically binds directly to the mTOR protein to fundamentally block its function. The research team verified this through molecular docking simulations (computer-based analysis of molecular interactions) and mass spectrometry (a technology that analyzes the mass and structure of molecules). The research team also confirmed that 13-HODE concentrations are extremely low in breast and colorectal cancer cells. This was found to be due to a decrease in the expression (the process by which genetic information is actually made into protein) of the ALOX15 enzyme required for 13-HODE generation. The research team proved that increasing the production of ALOX15 and 13-HODE reduces mTOR activity and suppresses cancer cell growth. Professor Seyun Kim said, "This research is significant in that it revealed that lipid metabolites generated within the human body can directly inhibit mTOR, a core protein for cancer growth. It can be utilized not only for new anticancer treatment strategies leveraging lipid metabolism but also for developing treatments that regulate mTOR overactivation observed during inflammation and aging processes."

Professor Young-Joo Byun from the College of Pharmacy at Korea University, who co-led the joint research, said, "This research is a study that clarified the interaction between proteins and fatty acid metabolites at the molecular level through the convergence of biological sciences and pharmacy. It will serve as an important foundation for the development of innovative new drugs in the future." Professor Jie Chen from the University of Illinois, USA, a world-renowned authority in the field of mTOR research, evaluated it in a journal preview as "an outstanding discovery that presents a new breakthrough in cancer cell control." This research, with Dr. Seung Ju Park and Ph.D. student Sera Kim from the Department of Biological Sciences at KAIST participating as co-first authors, and Professor Young-Joo Byun from the College of Pharmacy at Korea University and Professor Seyun Kim from the Department of Biological Sciences at KAIST participating as co-corresponding authors, was published on May 21st in the international academic journal in the field of chemical biology, Cell Chemical Biology. Furthermore, in recognition of its importance, it was selected as the cover article for the May issue of the journal. ※ Paper Title: Mechanism by which a linoleic acid metabolite suppresses cancer cell growth by inhibiting mTOR, DOI: https://doi.org/10.1016/j.chembiol.2026.04.004 ※ Author Information: Seung Ju Park, Sera Kim, Hongmok Kwon, Jiyeon Choi, Ji Kwang Kim, Inhong Jung, Seol-Wa Lim, Young Ran Kim, A-Yeong Yang, Boah Lee, Haein Lee, Seung Eun Park, Seulgi Lee, Myeongsu Shin, Bernie Byunghoon Park, YunHye Kim, Jinwook Lee, Byung-Chul Oh, Daniel Deredge, Patrick L. Wintrode, … Seyun Kim

< Cover Article of the Journal Cell Chemical Biology May Issue > 

Meanwhile, this research was conducted with support from the Samsung Science and Technology Foundation, the Mid-Career Research Program, the Basic Research Laboratory of the National Research Foundation of Korea, the Leading Research Center, the KAIST Quantum+X Interdisciplinary Convergence Technology Development Project, the KAIST Grand Challenge Project, and the Ministry of Education's Core Research Institute Program.