YAP1 Induces Invadopodia Formation by Transcriptionally Activating TIAM1 Through the Enhancer in Breast Cancer

Abstract

Yes-associated protein 1 (YAP1), a central component of the Hippo pathway, plays an important role in tumor metastasis; however, the mechanism remains to be elucidated. Here, we reported that YAP1 could induce invadopodia formation and promote tumor metastasis in breast cancer cells. We also identified TIAM1, the guanine nucleotide exchange factor, as a target of YAP1-TEAD4 complex. Our results demonstrated that YAP1 could promote TEAD4 binding to the enhancer region of TIAM1, which activated TIAM1 expression, and subsequently increased RAC1 activity and induced the invadopodia formation. These findings reveal the functional role of Hippo signaling in regulating invadopodia, and provide potential molecular targets for preventing tumor metastasis in breast cancer.