YAP and TAZ Take Center Stage in Cancer

Abstract

The Hippo pathway was originally identified and named through screening for mutations in Drosophila, and the core components of the Hippo pathway are highly conserved in mammals. In the Hippo pathway, MST1/2 and LATS1/2 regulate downstream transcription coactivators YAP and TAZ, which mainly interact with TEAD family transcription factors to promote tissue proliferation, self-renewal of normal and cancer stem cells, migration, and carcinogenesis. The Hippo pathway was initially thought to be quite straightforward; however, recent studies have revealed that YAP/TAZ is an integral part and a nexus of a network composed of multiple signaling pathways. Therefore, in this review, we will summarize the latest findings on events upstream and downstream of YAP/TAZ and the ways of regulation of YAP/TAZ. In addition, we also focus on the crosstalk between the Hippo pathway and other tumor-related pathways and discuss their potential as therapeutic targets.

Hippo signaling pathway transcription co-activator YAP is localized to podosomes/invadopodia in Src-transformed NIH-3T3 fibroblasts      

“…If yes, it would be important to check if other components of the Hippo signaling pathway are also involved in the formation of invadopodia. This could constitute another mechanism through which the Hippo signaling pathway impinges on cancer cell organization and metastasis [8] [9].…”

YAP and the Hippo pathway in pediatric cancer

“…5 However, YAP and TAZ are the main culprits in cancer pathogenesis, mainly through their interaction with the TEAD family of transcription factors. 12 The exact mechanism of YAP in cancer development is still under investigation. Many previous studies have reported elevated YAP protein levels in various types of cancer, such as colorectal, gastric, and human hepatocellular carcinoma.…”

“…Many previous studies have reported elevated YAP protein levels in various types of cancer, such as colorectal, gastric, and human hepatocellular carcinoma. 12,13 In this context, YAP is often described as an oncogene and its increased expression in cancers correlates with poor prognosis. For example, increased YAP expression is associated with high clinical stage and short overall survival in colorectal and ovarian cancer.…”

The emerging role of YAP/TAZ in mechanotransduction

“…Is activation of YAP/TAZ associated with endothelial apoptosis and enhanced lipid uptake in the vessel wall? What is the role of other known signalling pathways interacting with YAP/TAZ such as the Wnt pathway that was recently shown to be regulated by blood flow (12)(13)(14)? …”