YAP and TAZ Take Center Stage in Cancer
Kun Zhang1, Hai-Xia Qi2, Zhi-Mei Hu1
1Department of Histology and Embryology, School of Basic Medical Sciences, Tianjin Medical University , 300070 Tianjin, China.
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.
Insights
The Hippo pathway, involving MST1/2, LATS1/2, YAP, and TAZ, regulates cell growth and is crucial in cancer. This review explores its complex network and therapeutic potential.
Area of Science:
- Cell Biology
- Molecular Biology
- Oncology
Background:
- The Hippo pathway, conserved in mammals, regulates cell proliferation and stem cell self-renewal via MST1/2, LATS1/2, and YAP/TAZ.
- YAP/TAZ interact with TEAD transcription factors, influencing tissue growth, migration, and carcinogenesis.
- Recent findings reveal YAP/TAZ as a nexus in a complex signaling network, moving beyond its initial perception.
Purpose of the Study:
- To review recent findings on upstream and downstream events of YAP/TAZ.
- To summarize the regulatory mechanisms of YAP/TAZ.
- To explore the crosstalk between the Hippo pathway and other tumor-related pathways.
Main Methods:
- Literature review of recent studies on the Hippo pathway.
- Analysis of signaling networks involving YAP/TAZ.
- Discussion of potential therapeutic targets.
Main Results:
- The Hippo pathway's core components (MST1/2, LATS1/2) regulate YAP/TAZ.
- YAP/TAZ are key mediators of proliferation, stemness, migration, and carcinogenesis.
- YAP/TAZ function as a central hub integrating multiple signaling pathways.
Conclusions:
- The Hippo pathway is a complex network critical for normal development and cancer.
- Understanding YAP/TAZ regulation and pathway crosstalk is essential for therapeutic strategies.
- Targeting the Hippo pathway and its interactions offers promising avenues for cancer treatment.
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