YAP drives cell competition by activating choline metabolism

Cell competition is a phenomenon that eliminates unfit cells from cell society, a function vital for maintaining cellular and organismal homeostasis. We previously showed that Madin-Darby canine kidney (MDCK) epithelial cells expressing the active form of the transcriptional coactivator Yes-associated protein (YAP) are apically extruded when surrounded by normal MDCK cells. Although we demonstrated that the arachidonic acid (AA) cascade is involved in YAP-dependent apical extrusion, the metabolic events leading to this outcome remained unclear. Here, we present the results of metabolomic analysis that identified phosphatidylcholine (PC) biosynthesis as the most significant player in this process. Removal of the PC biosynthetic components choline and methionine from culture medium inhibited YAP-dependent apical extrusion. Inhibition of either choline uptake or metabolic cycles involving choline or methionine also decreased YAP-dependent apical extrusion. At the molecular level, active YAP induced expression of the genes encoding glycerophosphocholine phosphodiesterase 1 (GPCPD1) and lecithinecholesterol acyltransferase (LCAT), which are involved in choline metabolism. Our results indicate that YAP-dependent cell competition depends on YAP-mediated activation of the choline metabolic cycle. (C) 2021 The Authors. Published by Elsevier Inc.

Automated summary

The study reveals the importance of phosphatidylcholine biosynthesis in YAP-dependent cell competition, indicating that the activation of the choline metabolic cycle plays a crucial role in regulating cellular competition and extrusion.