scholarly journals The Emerging Role of the Hippo Pathway in Cell Contact Inhibition, Organ Size Control, and Cancer Development in Mammals

Cancer Cell ◽  
2008 ◽  
Vol 13 (3) ◽  
pp. 188-192 ◽  
Author(s):  
Qi Zeng ◽  
Wanjin Hong
Keyword(s):  
Hippo Pathway ◽  
Size Control ◽  
Organ Size ◽  
Contact Inhibition ◽  
Cancer Development ◽  
Cell Contact ◽  
The Hippo Pathway

scholarly journals Localized JNK signaling regulates organ size during development

eLife ◽  
2016 ◽  
Vol 5 ◽  
Author(s):  
Helen Rankin Willsey ◽  
Xiaoyan Zheng ◽  
José Carlos Pastor-Pareja ◽  
A Jeremy Willsey ◽  
Philip A Beachy ◽  
...  
Keyword(s):  
Hedgehog Signaling ◽  
Hippo Pathway ◽  
Size Control ◽  
Organ Size ◽  
Control Mechanisms ◽  
Cancer Therapies ◽  
Independent Manner ◽  
Jnk Signaling ◽  
New Strategy ◽  
The Hippo Pathway

A fundamental question of biology is what determines organ size. Despite demonstrations that factors within organs determine their sizes, intrinsic size control mechanisms remain elusive. Here we show that Drosophila wing size is regulated by JNK signaling during development. JNK is active in a stripe along the center of developing wings, and modulating JNK signaling within this stripe changes organ size. This JNK stripe influences proliferation in a non-canonical, Jun-independent manner by inhibiting the Hippo pathway. Localized JNK activity is established by Hedgehog signaling, where Ci elevates dTRAF1 expression. As the dTRAF1 homolog, TRAF4, is amplified in numerous cancers, these findings provide a new mechanism for how the Hedgehog pathway could contribute to tumorigenesis, and, more importantly, provides a new strategy for cancer therapies. Finally, modulation of JNK signaling centers in developing antennae and legs changes their sizes, suggesting a more generalizable role for JNK signaling in developmental organ size control.

scholarly journals The Hippo Pathway: Biology and Pathophysiology

2019 ◽  
Vol 88 (1) ◽  
pp. 577-604 ◽  
Author(s):  
Shenghong Ma ◽  
Zhipeng Meng ◽  
Rui Chen ◽  
Kun-Liang Guan
Keyword(s):  
Molecular Mechanisms ◽  
Hippo Pathway ◽  
Size Control ◽  
Tissue Growth ◽  
Cell Contact ◽  
Energy Status ◽  
Downstream Effectors ◽  
Kinase Cascade ◽  
Fate Decision ◽  
The Hippo Pathway

The Hippo pathway was initially discovered in Drosophila melanogaster as a key regulator of tissue growth. It is an evolutionarily conserved signaling cascade regulating numerous biological processes, including cell growth and fate decision, organ size control, and regeneration. The core of the Hippo pathway in mammals consists of a kinase cascade, MST1/2 and LATS1/2, as well as downstream effectors, transcriptional coactivators YAP and TAZ. These core components of the Hippo pathway control transcriptional programs involved in cell proliferation, survival, mobility, stemness, and differentiation. The Hippo pathway is tightly regulated by both intrinsic and extrinsic signals, such as mechanical force, cell–cell contact, polarity, energy status, stress, and many diffusible hormonal factors, the majority of which act through G protein–coupled receptors. Here, we review the current understanding of molecular mechanisms by which signals regulate the Hippo pathway with an emphasis on mechanotransduction and the effects of this pathway on basic biology and human diseases.

scholarly journals Cultured cells and wing disc size of silkworm can be controlled by the Hippo pathway

Open Biology ◽  
2018 ◽  
Vol 8 (7) ◽  
pp. 180029 ◽  
Author(s):  
Zi Liang ◽  
Yahong Lu ◽  
Ying Qian ◽  
Liyuan Zhu ◽  
Sulan Kuang ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Cultured Cells ◽  
Hippo Pathway ◽  
Size Control ◽  
Wing Disc ◽  
Organ Size ◽  
Promote Cell Proliferation ◽  
A Cell ◽  
The Hippo Pathway ◽  
Disc Size

Hippo signalling represents a cell proliferation and organ-size control pathway. Yorki (Yki), a component of the Hippo pathway, induces the transcription of a number of targets that promote cell proliferation and survival. The functions of Yki have been characterized in Drosophila and mammals, while there are few reports on silkworm, Bombyx mori . In the present study, we found that BmYki3 facilitates cell migration and cell division, and enlarges the cultured cell and wing disc size. Co-immunoprecipitation results indicated that BmYki3 may interact with thymosin, E3 ubiquitin-protein ligase, protein kinase ASK1, dedicator of cytokinesis protein 1, calcium-independent phospholipase A2 and beta-spectrin. RNA-seq results indicated that 4444 genes were upregulated and 10 291 genes were downregulated after BmYki3 was overexpressed in the cultured cells. GO annotation indicated that the up/downregulated genes were enriched in 268/382 GO terms ( p < 0.01); KEGG analysis showed that the up/downregulated genes were enriched in 49/101 pathways. These findings provided novel information to understand the functions of BmYki3 in a cell proliferation and organ-size control pathway.

scholarly journals Inactivation of YAP oncoprotein by the Hippo pathway is involved in cell contact inhibition and tissue growth control

2007 ◽  
Vol 21 (21) ◽  
pp. 2747-2761 ◽  
Author(s):  
B. Zhao ◽  
X. Wei ◽  
W. Li ◽  
R. S. Udan ◽  
Q. Yang ◽  
...  
Keyword(s):  
Hippo Pathway ◽  
Growth Control ◽  
Tissue Growth ◽  
Contact Inhibition ◽  
Cell Contact ◽  
The Hippo Pathway

scholarly journals Pits and CtBP control tissue growth in Drosophila melanogaster with the Hippo pathway transcription repressor, Tgi

2019 ◽  
Author(s):  
Joseph H.A. Vissers ◽  
Lucas G. Dent ◽  
Colin House ◽  
Shu Kondo ◽  
Kieran F. Harvey
Keyword(s):  
Cell Fate ◽  
Transcriptional Repression ◽  
Target Genes ◽  
Affinity Purification ◽  
Hippo Pathway ◽  
Transcriptional Response ◽  
Size Control ◽  
Tissue Growth ◽  
Organ Size ◽  
The Hippo Pathway

ABSTRACTThe Hippo pathway is an evolutionary conserved signalling network that regulates organ size, cell fate control and tumorigenesis. In the context of organ size control, the pathway incorporates a large variety of cellular cues such as cell polarity and adhesion into an integrated transcriptional response. The central Hippo signalling effector is the transcriptional co-activator Yorkie, which controls gene expression in partnership with different transcription factors, most notably Scalloped. When it is not activated by Yorkie, Scalloped can act as a repressor of transcription, at least in part due to its interaction with the corepressor protein Tgi. The mechanism by which Tgi represses transcription is incompletely understood and therefore we sought to identify proteins that potentially operate together with it. Using an affinity purification and mass-spectrometry approach we identified Pits and CtBP as Tgi-interacting proteins, both of which have been linked to transcriptional repression. Both Pits and CtBP were required for Tgi to suppress the growth of the D. melanogaster eye and CtBP loss suppressed the undergrowth of yorkie mutant eye tissue. Furthermore, as reported previously for Tgi, overexpression of Pits suppressed transcription of Hippo pathway target genes. These findings suggest that Tgi might operate together with Pits and CtBP to repress transcription of genes that normally promote tissue growth. The human orthologues of Tgi, CtBP and Pits (VGLL4, CTBP2 and IRF2BP2) physically and functionally interact to control transcription, implying that the mechanism by which these proteins control transcriptional repression is conserved throughout evolution.

scholarly journals The Hippo-Yes Association Protein Pathway in Liver Cancer

2013 ◽  
Vol 2013 ◽  
pp. 1-7 ◽  
Author(s):  
Lu Jie ◽  
Wang Fan ◽  
Dai Weiqi ◽  
Zhou Yingqun ◽  
Xu Ling ◽  
...  
Keyword(s):  
Liver Cancer ◽  
Hippo Pathway ◽  
Tumor Development ◽  
Size Control ◽  
Organ Size ◽  
Regulation Of Transcription ◽  
Hippo Signaling ◽  
Evolutionary Changes ◽  
Kinase Cascade ◽  
The Hippo Pathway

Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide and the third leading cause of cancer mortality. Despite continuing development of new therapies, prognosis for patients with HCC remains extremely poor. In recent years, control of organ size becomes a hot topic in HCC development. The Hippo signaling pathway has been delineated and shown to be critical in controlling organ size in both Drosophila and mammals. The Hippo kinase cascade, a singling pathway that antagonizes the transcriptional coactivator Yes-associated protein (YAP), plays an important role in animal organ size control by regulating cell proliferation and apoptosis rates. During HCC development, this pathway is likely inactivated in tumor initiated cells that escape suppressive constrain exerted by the surrounding normal tissue, thus allowing clonal expansion and tumor development. We have reviewed evolutionary changes in YAP as well as other components of the Hippo pathway and described the relationships between YAP genes and HCC. We also discuss regulation of transcription factors that are up- and downstream of YAP in liver cancer development.

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