Data from A Wnt-Independent LGR4–EGFR Signaling Axis in Cancer Metastasis

• DOI: 10.1158/0008-5472.c.6513421.v1
• Publication Date: 2023-03-31T21:20:41Z
• Authors: Fei Yue; Weiyu Jiang; Amy T. Ku; Adelaide I.J. Young; Weijie Zhang; Eric P. Souto; Yankun Gao; Zihan Yu; Yi Wang; Chad J. Creighton; Chandandeep Nagi; Tao Wang; Susan G. Hilsenbeck; Xin-Hua Feng; Shixia Huang; Cristian Coarfa; Xiang H.-F. Zhang; Qingyun Liu; Xia Lin; Yi Li

<div>Abstract<p>Leucine-rich repeat-containing G protein–coupled receptors 4, 5, and 6 (LGR4/5/6) play critical roles in development cancer. The widely accepted mechanism is that these proteins, together with their R-spondin ligands, stabilize Wnt receptors, thus potentiating signaling. Here we show LGR4 enhanced breast cancer cell metastasis even when signaling was deactivated pharmacologically or genetically. Furthermore, mutants cannot potentiate nevertheless promoted migration invasion <i>in vitro</i> vivo</i>. Multiomic screening identified EGFR as a crucial mediator of activity progression. Mechanistically, interacted blocked ubiquitination degradation, resulting persistent activation. Together, data uncover Wnt-independent LGR4–EGFR axis broad implications for progression targeted therapy.</p>Significance:<p>This work demonstrates by which promotes metastasis.</p><p><i>See related commentary Stevens Williams, p. 4397</i></p></div>