The Hippo Signaling Pathway in Development and Cancer

By Duojia Pan. Developmental Cell, 2010

2,291 citations recorded by the source corpus.

First discovered in Drosophila, the Hippo signaling pathway is a conserved regulator of organ size. Central to this pathway is a kinase cascade leading from the tumor suppressor Hippo (Mst1 and Mst2 in mammals) to the oncoprotein Yki (YAP and TAZ in mammals), a transcriptional coactivator of target genes involved in cell proliferation and survival. Here, I review recent progress in elucidating the molecular mechanism and physiological function of Hippo signaling in Drosophila and mammals. These studies suggest that the core Hippo kinase cascade integrates multiple upstream inputs, enabling dynamic regulation of tissue homeostasis in animal development and physiology.

Subfields: Cell Biology

View Paper: https://www.semanticscholar.org/paper/007b573a0a79c83235a248a27a6ad93ccbcb3f91

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In Cell Biology

1. K. Guan
2. S. Piccolo
3. Fa-Xing Yu
4. Bin Zhao
5. M. Cordenonsi
6. H. Park
7. Jung-Soon Mo
8. S. Dupont

Citations in the corpus

• The biology of YAP/TAZ: hippo signaling and beyond. (2014, background): “The function of LATS/warts remained rather poorly investigated until 2003, when other core components of the Hippo cascade were identified by similar screens (61, 64, 74, 80, 168).”
• Role of YAP/TAZ in mechanotransduction (2011, background): “Genetically, YAP and TAZ have been linked to a universal system that controls organ size 14 .”
• Cell detachment activates the Hippo pathway via cytoskeleton reorganization to induce anoikis. (2012, background): “…cells Accumulating evidence supports an oncogenic role of YAP and a tumor suppressor function of the Hippo pathway (Overholtzer et al. 2006; Zender et al. 2006; Zhao et al. 2007; Steinhardt et al. 2008; Xu et al. 2009; Zhou et al. 2009; Lee et al. 2010; Lu et al. 2010; Pan 2010; Song et al. 2010).”
• E-cadherin mediates contact inhibition of proliferation through Hippo signaling-pathway components (2011, background): “The protein kinase cascade of the Hippo signaling pathway stimulates the nuclear exclusion and inactivation of transcriptional coactivator Yes-associated protein (YAP) and its paralog TAZ (transcriptional activator with PDZ binding motif) (19).”
• Hippo pathway effector Yap promotes cardiac regeneration (2013, background): “Hippo, Salvador, Mats, and Yorkie are structurally and functionally orthologous to mammalian Mst1/2, Sav1, Lats1/2, and Yap/Taz, respectively, and many of these mammalian Hippo signaling components have been implicated in the control of organ size and tumorigenesis (20, 21, 30, 31).”
• YAP/TAZ at the roots of cancer (2016, background): “…components causes organ to grow well beyond their normal size up to a ostensible preneoplastic state; and yet this is a reversible condition, as when the YAP/TAZ inducing stimuli is interrupted, the big organ shrinks back to its correct size, losing the excess of cells by apoptosis (Pan, 2010).”
• The Hippo pathway in organ size control, tissue regeneration and stem cell self-renewal (2011, positive): “Extensive research led to the identification of the Hippo tumour-suppressor pathway as a key regulator of organ size in Drosophila and mammal”
• The Hippo signaling pathway in stem cell biology and cancer (2014, positive): “As discussed above, the Hippo pathway plays a key role in regulating organ size and tumorigenesis by inhibiting cell proliferation, promoting apoptosis, and regulating stem/progenitor cell expansion [134,135].”
• Hippo Pathway in Organ Size Control, Tissue Homeostasis, and Cancer. (2015, positive): “) leads to overgrowth of organs such as eyes, wings, or other appendages, and transgenic expression of yki results in a similar phenotype (reviewed in Halder and Johnson, 2011; Pan, 2010).”
• YAP/TAZ incorporation in the β-catenin destruction complex orchestrates the Wnt response. (2014, background): “Second, we considered a main mechanism by which YAP/TAZ are normally retained in the nucleus, that is, inactivation of the Hippo pathway leading to nuclear YAP/TAZ associated with TEAD (Pan, 2010).”
• The Hippo pathway: regulators and regulations. (2013, background): “2; for reviews, see Pan 2010; Zhao et al. 2010a).”
• The Hippo transducer TAZ confers cancer stem cell-related traits on breast cancer cells. (2011, background): “TAZ and YAP are central mediators of the Hippo pathway, which regulates organ size from Drosophila to mammals (Pan, 2010).”
• A mechanical checkpoint controls multicellular growth through YAP/TAZ regulation by actin-processing factors. (2013, positive): “…to investigate the intersections between the control of YAP/TAZ activity by cytoskeletal cues and the classical Hippo cascade, centered on the activity of two kinases, MST1/ 2 (Hippo in Drosophila) and LATS1/2, the latter directly phosphorylating YAP/TAZ and causing their inhibition (Pan, 2010).”
• KRAS and YAP1 converge to regulate EMT and tumor survival (2014, background): “YAP1 serves as an effector of the Hippo (Hpo) kinase cascade and regulates the Transcriptional Enhancer Activator Domain (TEAD) transcription factors (Pan, 2010).”