YAP controls cell migration and invasion through a Rho-GTPase switch

Delineating the mechanisms controlling the invasive spread of non-diseased and transformed cells is central to understanding diverse processes including cancer progression. Here, we found that Yes-associated protein (YAP), a central transcriptional regulator implicated in controlling organ and body size, modulated a Rho-GTPase switch that drives cellular migration by transactivating the Rac1-GEF protein TRIO through direct modulation of its intronic enhancer. Additionally, YAP and TRIO may promote invasive behavior through putative crosstalk with STAT3 signaling, a potential downstream target. Although we found this YAP-dependent infiltrative program in many cell types, it was particularly enhanced in a patient-specific manner in the most common malignant brain tumor, glioblastoma (GBM), where hyperactivation of the YAP, TRIO, and STAT3 signatures also conferred poor clinical outcome. Our analysis suggests that the YAP-TRIO-Rho-GTPase signaling network identified in this study is a ubiquitous regulator of invasive cell spread in both physiological and pathological contexts. In this dataset, we knocked down YAP in two patient-derived GBM primary cell lines (JHGB612 and JHGB651) and performed microarray analysis. A total number of 12 samples were analyzed. JHGBM612 and JHGBM651 cells with stable knockdown of YAP (shYAP) and the empty backbone vector as a control (shCtrl), each with 3 replicates. shYAP and shCtrl cells were extracted for microarray analysis.