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Lysine is required for growth factor-induced mTORC1 activation
Se-Kyeong Jang1, Sung-Eun Hong2, Da-Hee Lee3
1Division of Fusion Radiology Research, Korea Institute of Radiological & Medical Sciences, 75 Nowon-ro, Nowon-gu, Seoul, 01812, Republic of Korea; Department of Food and Microbial Technology, Seoul Women's University, 621 Hwarangro, Nowon-gu, Seoul, 01797, Republic of Korea.
Biochemical and Biophysical Research Communications
|October 3, 2020
Summary
Lysine is crucial for activating mechanistic target of rapamycin complex 1 (mTORC1) in lung cancer cells. Its absence inhibits mTORC1, even with growth factors, highlighting lysine
Area of Science:
- Cellular metabolism
- Cancer biology
- Molecular signaling
Background:
- Mechanistic target of rapamycin complex 1 (mTORC1) regulates cell growth and metabolism.
- mTORC1 activity is sensitive to amino acid availability.
- Non-small cell lung cancer (NSCLC) cells exhibit altered metabolic pathways.
Purpose of the Study:
- To investigate the role of lysine in regulating mTORC1 activity in NSCLC cells.
- To determine if growth factors can activate mTORC1 in the absence of lysine.
- To identify signaling pathways involved in lysine-mediated mTORC1 regulation.
Main Methods:
- Lysine deprivation and replenishment experiments in NSCLC cells.
- Assessment of mTORC1 activity under various nutrient and growth factor conditions.
- Analysis of the involvement of General control nonderepressible 2 (GCN2) and AMP-activated protein kinase (AMPK).
Main Results:
- Lysine deprivation suppressed mTORC1 activity in NSCLC cells.
- Lysine replenishment restored mTORC1 activity.
- Growth factors could not fully restore mTORC1 activity in the absence of lysine.
- GCN2 and AMPK were implicated in lysine deprivation-induced mTORC1 inhibition.
Conclusions:
- Lysine plays a significant role in mTORC1 activation in NSCLC cells.
- Lysine availability is essential for efficient mTORC1 signaling, independent of growth factors.
- Targeting lysine metabolism may represent a therapeutic strategy for NSCLC.
Keywords:
AMP-Activated protein kinaseAmino acidGeneral control nonderepressible 2LysineMechanistic target of rapamycin complex 1More Related Videos
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