RagC senses β-hydroxybutyrate abundancy to suppress mTORC1 and tumor growth - PubMed
4 hours ago
- #mTORC1
- #ketogenic diet
- #colorectal cancer
- The ketogenic diet (KD) reprograms energy metabolism from glucose to ketone bodies, including β-hydroxybutyrate (BHB), acetoacetate (AcAc), and acetone (Ac).
- RagC, a component of the mTORC1 pathway, senses BHB to suppress tumor growth but does not respond to AcAc or Ac.
- BHB inhibits mTORC1 by promoting β-hydroxybutyrylation (Kbhb) of RagC at lysine 349 (K348 in mice).
- RagC-K349bhb is regulated by p300 (catalyzes) and SIRT1 (erases), disrupting RagC interaction with Raptor/mTOR and blocking mTORC1 recruitment to lysosomes.
- BHB-mediated RagC-K349bhb suppresses colorectal cancer (CRC) growth via mTORC1 inhibition in both mouse models and patient-derived samples.
- The study highlights RagC-K349bhb as a potential therapeutic target for BHB-based CRC treatment.