A Netrin-UNC5-ITGAV/B5 pathway mediates YAP-induced cytostasis. A–D, A netrin blocking antibody (α-NTN) or trapping reagent (UNC5-Fc) alleviates YAP-induced cytostasis in YAPoff cell lines. Cell lines and tumor types are indicated in each. Y79 cells expressed wild type YAP, whereas WERI-RB1, NCI-H209 and NCI-H2171 expressed YAP5SA. *, P < 0.05; **, P < 0.01; ***, P < 0.001 compared with untreated (untr) cells; n = 3–5 (A and B) or 3 (C and D). E, Rescue of YAP-induced cytostasis in control or UNC5B knockout Y79 cells treated with an Integrin-αV/β5 blocking antibody. *, P < 0.05 compared with untreated sgControl cells; n = 3. F, Summary of the mechanism of YAP-induced cytostasis in YAPoff cancers.
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Pearson et al. (2024) studied this question.
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