YAP1-TEAD1-Glut1 axis dictates the oncogenic phenotypes of breast cancer cells by modulating glycolysis

Altered energy metabolism is a universal property of most cancer cells. The Hippo signaling pathway and its principal downstream effector YAP1 are responsible for tissue homeostasis including organ size, cell proliferation, apoptosis, and differentiation. Dysregulation of the Hippo pathway leads to the activation of YAP1 and further culminates in the development of multiple human cancers. In this study, by loss-of-function assay, we demonstrated that YAP1 contributed to the glycolytic phenotype of breast cancer cells. Knockdown of YAP1 inhibited the extracellular acidification rates, glucose consumption, and lactate production of breast cancer cells. Moreover, YAP1 interacted with TEAD1, exerted their transcriptional control of the functional target, glucose transporter 1 (Glut1). Overexpression of Glut1 restored the inhibitory effects of YAP1 knockdown on glycolysis as demonstrated by glucose consumption and lactate production. Suppression of glycolysis by deprivation of glucose largely compromised the oncogenic roles of YAP1 on cell proliferation, apoptosis, and invasive potential. Taken together, our data identify a novel role of YAP1-TEAD1 pathway in cancer energy metabolism.