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All-optical Mechanobiology Interrogation of Yes-associated Protein in Human Cancer and Normal Cells using a Multi-functional System
Published on: December 20, 2021
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YAP drives cell competition by activating choline metabolism
Sachi Sunaga1, Satoshi Kofuji1, Hiroshi Nishina1
1Department of Developmental and Regenerative Biology, Medical Research Institute, Tokyo Medical and Dental University (TMDU), Tokyo, Japan.
Biochemical and Biophysical Research Communications
|August 10, 2021
Summary
Cell competition eliminates unfit cells, a process vital for homeostasis. This study reveals that active Yes-associated protein (YAP) triggers cell extrusion by activating the choline metabolic cycle.
Area of Science:
- Cell Biology
- Metabolomics
- Molecular Biology
Background:
- Cell competition is crucial for maintaining tissue homeostasis by eliminating unfit cells.
- Previous work identified arachidonic acid (AA) cascade involvement in Yes-associated protein (YAP)-dependent cell extrusion.
- The specific metabolic events driving YAP-dependent cell competition were previously unclear.
Purpose of the Study:
- To elucidate the metabolic mechanisms underlying YAP-dependent cell competition.
- To identify key metabolic pathways involved in the apical extrusion of YAP-overexpressing cells.
Main Methods:
- Metabolomic analysis of Madin-Darby canine kidney (MDCK) cells.
- Manipulation of culture medium components (choline, methionine).
- Inhibition of choline uptake and related metabolic cycles.
- Gene expression analysis of YAP-regulated enzymes.
Main Results:
- Phosphatidylcholine (PC) biosynthesis was identified as a critical metabolic pathway.
- Depletion of choline or methionine from the medium significantly reduced YAP-dependent apical extrusion.
- Inhibition of choline uptake or metabolic cycles impaired cell extrusion.
- Active YAP upregulated genes for GPCPD1 and LCAT, enzymes in choline metabolism.
Conclusions:
- YAP-dependent cell competition is critically regulated by the activation of the choline metabolic cycle.
- YAP directly influences choline metabolism to promote the elimination of less fit cells.
- This study highlights the link between YAP signaling, choline metabolism, and cell competition.
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