Multifaceted regulation and functions of YAP/TAZ in tumors

The Hippo pathway, initially identified through screenings for mutant tumor suppressors in Drosophila, is an evolutionarily conserved signaling pathway that controls organ size by regulating cell proliferation and apoptosis. Abnormal regulation of the Hippo pathway may lead to cancer in mammals. As the major downstream effectors of the Hippo pathway, unphosphorylated Yes-associated protein (YAP) and its homolog transcriptional co-activator TAZ (also called WWTR1) (hereafter called YAP/TAZ) are translocated into the nucleus. In the nucleus, in order to induce target gene expression, YAP/TAZ bind to the TEA domain (TEAD) proteins, and this binding subsequently promotes cell proliferation and inhibits apoptosis. In contrast, as key regulators of tumorigenesis and development, YAP/TAZ are phosphorylated and regulated by multiple molecules and pathways including Lats1/2 of Hippo, Wnt and G-protein-coupled receptor (GPCR) signaling, with a regulatory role in cell physiology, tumor cell development and pathological abnormalities simultaneously. In particular, the crucial role of YAP/TAZ in tumors ensures their potential as targets in designing anticancer drugs. To date, mounting research has elucidated the suppression of YAP/TAZ via effective inhibitors, which significantly highlights their application in cancer treatment. In the present review, we focus on the functions of YAP/TAZ in cancer, discuss their potential as new therapeutic target for tumor treatment, and provide valuable suggestions for further study in this field.