Control of stem cell renewal and fate by YAP and TAZ

被引:78
作者
Driskill, Jordan H. [1 ]
Pan, Duojia [1 ]
机构
[1] Univ Texas Southwestern Med Ctr, Howard Hughes Med Inst, Dept Physiol, Dallas, TX 75390 USA
基金
美国国家卫生研究院;
关键词
EPITHELIAL-MESENCHYMAL TRANSITION; HIPPO SIGNALING PATHWAY; AMPK-MEDIATED REGULATION; GENOME-WIDE ASSOCIATION; TUMOR-SUPPRESSOR; SELF-RENEWAL; CARDIOMYOCYTE PROLIFERATION; INTESTINAL REGENERATION; TRANSCRIPTIONAL OUTPUT; PROMOTES APOPTOSIS;
D O I
10.1038/s41580-023-00644-5
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Complex physiological processes control whether stem cells self-renew, differentiate or remain quiescent. Two decades of research have placed the Hippo pathway, a highly conserved kinase signalling cascade, and its downstream molecular effectors YAP and TAZ at the nexus of this decision. YAP and TAZ translate complex biological cues acting on stem cells - from mechanical forces to cellular metabolism - into genome-wide effects to mediate stem cell functions. While aberrant YAP/TAZ activity drives stem cell dysfunction in ageing, tumorigenesis and disease, therapeutic targeting of Hippo signalling and YAP/TAZ can boost stem cell activity to enhance regeneration. In this Review, we discuss how YAP/TAZ control the self-renewal, fate and plasticity of stem cells in different contexts, how dysregulation of YAP/TAZ in stem cells leads to disease, and how therapeutic modalities targeting YAP/TAZ may benefit regenerative medicine and cancer therapy. YAP and TAZ are transcription coactivators with key roles in development and regeneration as well as in cancer. Many of these roles are executed by YAP/TAZ activation in stem cells. This Review discusses how YAP/TAZ regulate stem cell biology, and considers potential applications of modulating YAP/TAZ in regenerative medicine and cancer therapy.
引用
收藏
页码:895 / 911
页数:17
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