Related Experiment Video
Updated: Mar 20, 2026
06:51
Utilizing 18F-FDG PET/CT Imaging and Quantitative Histology to Measure Dynamic Changes in the Glucose Metabolism in Mouse Models of Lung Cancer
Published on: July 21, 2018
18.8K
RagC senses β-hydroxybutyrate abundancy to suppress mTORC1
Guoyan Wang1, Qihang Hou1, Yong Zhang2
1College of Animal Science and Technology, Northwest A&F University, Yangling 712100, China.
Protein & Cell
|March 18, 2026
Summary
The ketogenic diet uses beta-hydroxybutyrate (BHB) to suppress tumor growth by inhibiting the mTORC1 pathway. This study identifies BHB sensing by RagC, a key mTORC1 component, offering a new therapeutic target for colorectal cancer.
Area of Science:
- Biochemistry
- Oncology
- Metabolic pathways
Background:
- The ketogenic diet (KD) reprograms cellular metabolism from glucose to ketone bodies.
- Mechanisms linking ketone body signaling to tumor suppression are not fully understood.
Purpose of the Study:
- To elucidate how ketone body signals are sensed to suppress tumor growth.
- To identify the specific ketone body and molecular players involved in this process.
Main Methods:
- Investigated the role of RagC in sensing ketone bodies.
- Utilized biochemical assays to study the effect of beta-hydroxybutyrate (BHB) on mTORC1 activity.
- Examined RagC modification (β-hydroxybutyrylation) and its impact on mTORC1 complex formation.
- Analyzed BHB-mediated RagC modification in mouse models and patient-derived colorectal cancer (CRC) samples.
Main Results:
- RagC senses BHB, but not acetoacetate (AcAc) or acetone (Ac), to inhibit tumor growth.
- BHB induces β-hydroxybutyrylation (Kbhb) of RagC at lysine 349, inhibiting mTORC1.
- This modification is regulated by p300 and SIRT1, affecting RagC-Raptor/mTOR interaction and lysosomal recruitment.
- BHB-mediated RagC-K349bhb suppresses CRC growth via mTORC1 inhibition.
Conclusions:
- Identified a novel BHB sensing mechanism involving RagC and mTORC1.
- RagC-K349bhb is a key mediator of KD's anti-tumor effects in CRC.
- RagC-K349bhb represents a potential therapeutic target for BHB-based CRC treatments.
Related Concept Videos
03:03mTOR Signaling and Cancer Progression
5.0K
The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
The mTOR pathway or the...
5.0K
03:03mTOR Signaling and Cancer Progression
1.6K
1.6K
01:22PI3K/mTOR/AKT Signaling Pathway
6.2K
The mammalian target of rapamycin (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1 (mTORC1) and mTOR complex 2 (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast, mTORC2 consists of a...
6.2K
02:38The Ras Gene
7.5K
The Ras-gene-encoded proteins are regulators of signaling pathways controlling cell proliferation, differentiation, or cell survival. The Ras-gene family in humans constitutes three primary members—the HRas, NRas, and KRas. These genes code for four functionally distinct yet closely related proteins—the HRas, NRas, KRas4A, and KRas4B. The involvement of mutant Ras genes in human cancer was first discovered in 1982 and is among the most common causes of human tumorigenesis.
Ras is a...
Ras is a...
7.5K
01:20The Retinoblastoma Gene
4.9K
Tumor suppressor genes are normal genes that can slow down cell division, repair DNA mistakes, or program the cells for apoptosis in case of irreparable damage. Hence, they play an essential role in preventing the proliferation of damaged cells.
The first-ever tumor suppressor gene called Rb was identified in retinoblastoma - a rare eye tumor in children. In inherited forms of the disease, a child inherits one defective copy of the Rb gene, which predisposes them to retinoblastoma. However,...
The first-ever tumor suppressor gene called Rb was identified in retinoblastoma - a rare eye tumor in children. In inherited forms of the disease, a child inherits one defective copy of the Rb gene, which predisposes them to retinoblastoma. However,...
4.9K
02:23Abnormal Proliferation
5.4K
Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the...
5.4K