The Hippo pathway in organ size control, tissue regeneration and stem cell self-renewal
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TLDR
Current understanding of the composition and regulation of the Hippo pathway is summarized, and how cell polarity and cell adhesion proteins inform the role of this pathway in organ size control and regeneration is discussed.Abstract:
Precise control of organ size is crucial during animal development and regeneration. In Drosophila and mammals, studies over the past decade have uncovered a critical role for the Hippo tumour-suppressor pathway in the regulation of organ size. Dysregulation of this pathway leads to massive overgrowth of tissue. The Hippo signalling pathway is highly conserved and limits organ size by phosphorylating and inhibiting the transcription co-activators YAP and TAZ in mammals and Yki in Drosophila, key regulators of proliferation and apoptosis. The Hippo pathway also has a critical role in the self-renewal and expansion of stem cells and tissue-specific progenitor cells, and has important functions in tissue regeneration. Emerging evidence shows that the Hippo pathway is regulated by cell polarity, cell adhesion and cell junction proteins. In this review we summarize current understanding of the composition and regulation of the Hippo pathway, and discuss how cell polarity and cell adhesion proteins inform the role of this pathway in organ size control and regeneration.read more
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Nuclear lamin-A Scales With Tissue Stiffness and Enhances Matrix-Directed Differentiation
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Mechanotransduction and YAP-dependent matrix remodelling is required for the generation and maintenance of cancer-associated fibroblasts
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Making new contacts: the mTOR network in metabolism and signalling crosstalk
TL;DR: Emerging evidence provides new insight into the control of mTOR by other pathways such as Hippo, WNT and Notch signalling, and this progress has expanded the list of downstream effectors and upstream regulators of m TOR signalling.
Journal ArticleDOI
Transduction of mechanical and cytoskeletal cues by YAP and TAZ
TL;DR: Cues from the extracellular matrix, cell adhesion sites, cell shape and the actomyosin cytoskeleton were found to converge on the regulation of the downstream effectors of the Hippo pathway YAP and TAZ in vertebrates and Yorkie in flies, which may explain how mechanical signals can direct normal and pathological cell behaviour.
Journal ArticleDOI
Hippo pathway effector Yap promotes cardiac regeneration
Mei Xin,Yuri Kim,Lillian B. Sutherland,Masao Murakami,Xiaoxia Qi,John McAnally,Enzo R. Porrello,Ahmed I. Mahmoud,Wei Tan,John M. Shelton,James A. Richardson,Hesham A. Sadek,Rhonda Bassel-Duby,Eric N. Olson +13 more
TL;DR: It is reported that mice bearing mutant alleles of Yap and its paralog WW domain containing transcription regulator 1 (Taz) exhibit gene dosage-dependent cardiac phenotypes, suggesting redundant roles of these Hippo pathway effectors in establishing proper myocyte number and maintaining cardiac function.
References
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Journal ArticleDOI
Inactivation of YAP oncoprotein by the Hippo pathway is involved in cell contact inhibition and tissue growth control
Bin Zhao,Xiaomu Wei,Weiquan Li,Ryan S. Udan,Ryan S. Udan,Qian Yang,Joungmok Kim,Joungmok Kim,Joe Xie,Tsuneo Ikenoue,Jindan Yu,Li Li,Li Li,Pan Zheng,Keqiang Ye,Arul M. Chinnaiyan,Georg Halder,Georg Halder,Zhi Chun Lai,Kun-Liang Guan,Kun-Liang Guan +20 more
TL;DR: It is demonstrated that in mammalian cells, the transcription coactivator YAP (Yes-associated protein), is inhibited by cell density via the Hippo pathway, and YAP overexpression regulates gene expression in a manner opposite to cell density, and is able to overcome cell contact inhibition.
Journal ArticleDOI
Elucidation of a universal size-control mechanism in Drosophila and mammals.
Jixin Dong,Georg Feldmann,Jianbin Huang,Shian Wu,Nailing Zhang,Sarah A. Comerford,Mariana F. Gayyed,Robert A. Anders,Anirban Maitra,Duojia Pan +9 more
TL;DR: It is demonstrated that a single phosphorylation site in Yki mediates the growth-suppressive output of the Hippo pathway, and that its dysregulation leads to tumorigenesis, uncovering a universal size-control mechanism in metazoan.
Journal ArticleDOI
The Hippo Signaling Pathway in Development and Cancer
TL;DR: Recent studies suggest that the core Hippo kinase cascade integrates multiple upstream inputs, enabling dynamic regulation of tissue homeostasis in animal development and physiology.
Journal ArticleDOI
TEAD mediates YAP-dependent gene induction and growth control
Bin Zhao,Xin Ye,Jindan Yu,Li Li,Li Li,Weiquan Li,Siming Li,Jianjun Yu,Jiandie D. Lin,Cun-Yu Wang,Arul M. Chinnaiyan,Zhi Chun Lai,Kun-Liang Guan +12 more
TL;DR: TEAD is revealed as a new component in the Hippo pathway playing essential roles in mediating biological functions of YAP, and is required for YAP-induced cell growth, oncogenic transformation, and epithelial-mesenchymal transition.
Journal ArticleDOI
The Hippo Signaling Pathway Coordinately Regulates Cell Proliferation and Apoptosis by Inactivating Yorkie, the Drosophila Homolog of YAP
TL;DR: Yorkie (Yki), the Drosophila ortholog of the mammalian transcriptional coactivator yes-associated protein (YAP), is identified as a missing link between Wts and transcriptional regulation and is a critical target of the Wts/Lats protein kinase and a potential oncogene.