YAP activity is necessary and sufficient for basal progenitor abundance and proliferation in the developing neocortex

SummaryThe expansion of the neocortex during mammalian evolution has been linked to an enlargement of the subventricular zone during cortical development and an increase in the proliferation of the basal progenitors residing therein. Here, we explored a potential role of YAP, the major downstream effector of the Hippo signaling pathway, in proliferation of basal progenitors. We show that YAP expression and activity are high in ferret and human basal progenitors, which are known to exhibit high proliferative capacity, but low in mouse basal progenitors, which lack such capacity. To induce YAP activity in mouse basal progenitors, we expressed a constitutively active YAP (CA-YAP). This resulted in an increase in proliferation of basal progenitor. In addition, CA-YAP expressing mouse basal progenitors promoted the production of upper-layer neurons. To investigate if YAP is required for the proliferation of basal progenitors, we pharmacologically interfered with the function of YAP in the developing ferret and human neocortex. This resulted in a decrease of cycling basal progenitors. In concert, genetical interference with the function of YAP in ferret developing neocortex resulted in decreased abundance of basal progenitors. Together, our data indicate that YAP promotes the proliferation of basal progenitors and suggest that changes in YAP activity levels contributed to the evolutionary expansion of the neocortex.

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Potential Role of Hippo-Signaling Pathway in Gastric Cancer

OALib ◽

10.4236/oalib.1102481 ◽

2016 ◽

Vol 03 (03) ◽

pp. 1-7

Author(s):

Noman Ali ◽

Muhammad Asim ◽

Raheel Asghar ◽

Awais Amin ◽

Muhammad Saif Ur Rahman

Keyword(s):

Gastric Cancer ◽

Signaling Pathway ◽

Potential Role ◽

Hippo Signaling ◽

Hippo Signaling Pathway

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Hsa_circ_0005273 facilitates breast cancer tumorigenesis by regulating YAP1-hippo signaling pathway

Journal of Experimental & Clinical Cancer Research ◽

10.1186/s13046-021-01830-z ◽

2021 ◽

Vol 40 (1) ◽

Author(s):

Xuehui Wang ◽

Changle Ji ◽

Jiashu Hu ◽

Xiaochong Deng ◽

Wenfang Zheng ◽

...

Keyword(s):

Breast Cancer ◽

Signaling Pathway ◽

Cell Lines ◽

Luciferase Reporter ◽

Circular Rnas ◽

Hippo Signaling ◽

Hippo Signaling Pathway ◽

Potential Biomarker

Abstract Background Circular RNAs (circRNAs), a novel class of endogenous RNAs, have shown to participate in the development of breast cancer (BC). Hsa_circ_0005273 is a circRNA generated from several exons of PTK2. However, the potential functional role of hsa_circ_0005273 in BC remains largely unknown. Here we aim to evaluate the role of hsa_circ_0005273 in BC. Methods The expression level of hsa_circ_0005273 and miR-200a-3p were examined by RT-qPCR in BC tissues and cell lines. The effect of knocking down hsa_circ_0005273 in BC cell lines were evaluated by examinations of cell proliferation, migration and cell cycle. In addition, xenografts experiment in nude mice were performed to evaluate the effect of hsa_circ_0005273 in BC. RNA immunoprecipitation assay, RNA probe pull-down assay, luciferase reporter assay and fluorescence in situ hybridization were conducted to confirm the relationship between hsa_circ_0005273, miR-200a-3p and YAP1. Results Hsa_circ_0005273 is over-expressed in BC tissues and cell lines, whereas miR-200a-3p expression is repressed. Depletion of hsa_circ_0005273 inhibited the progression of BC cells in vitro and in vivo, while overexpression of hsa_circ_0005273 exhibited the opposite effect. Importantly, hsa_circ_0005273 upregulated YAP1 expression and inactivated Hippo pathway via sponging miR-200a-3p to promote BC progression. Conclusions Hsa_circ_0005273 regulates the miR-200a-3p/YAP1 axis and inactivates Hippo signaling pathway to promote BC progression, which may become a potential biomarker and therapeutic target.

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Role of Hippo signaling pathway in early placental development

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.2013559117 ◽

2020 ◽

Vol 117 (34) ◽

pp. 20354-20356

Author(s):

Francesca Soncin ◽

Mana M. Parast

Keyword(s):

Signaling Pathway ◽

Hippo Signaling ◽

Placental Development ◽

Hippo Signaling Pathway

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The emerging role of Hippo signaling pathway in regulating osteoclast formation

Journal of Cellular Physiology ◽

10.1002/jcp.26372 ◽

2018 ◽

Vol 233 (6) ◽

pp. 4606-4617 ◽

Cited By ~ 20

Author(s):

Wanlei Yang ◽

Weiqi Han ◽

An Qin ◽

Ziyi Wang ◽

Jiake Xu ◽

...

Keyword(s):

Signaling Pathway ◽

Osteoclast Formation ◽

Hippo Signaling ◽

Hippo Signaling Pathway

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The fate of the primary cilium during myofibroblast transition

Molecular Biology of the Cell ◽

10.1091/mbc.e13-07-0429 ◽

2014 ◽

Vol 25 (5) ◽

pp. 643-657 ◽

Cited By ~ 15

Author(s):

Matthew Rozycki ◽

Monika Lodyga ◽

Jessica Lam ◽

Maria Zena Miranda ◽

Károly Fátyol ◽

...

Keyword(s):

Growth Factor ◽

Sonic Hedgehog ◽

Primary Cilium ◽

Potential Role ◽

Transforming Growth Factor ◽

Transforming Growth Factor Β1 ◽

Related Transcription Factor ◽

Necessary And Sufficient ◽

Organ Fibrosis

Myofibroblasts, the culprit of organ fibrosis, can originate from mesenchymal and epithelial precursors through fibroblast–myofibroblast and epithelial–myofibroblast transition (EMyT). Because certain ciliopathies are associated with fibrogenesis, we sought to explore the fate and potential role of the primary cilium during myofibroblast formation. Here we show that myofibroblast transition from either precursor results in the loss of the primary cilium. During EMyT, initial cilium growth is followed by complete deciliation. Both EMyT and cilium loss require two-hit conditions: disassembly/absence of intercellular contacts and transforming growth factor-β1 (TGFβ) exposure. Loss of E-cadherin–dependent junctions induces cilium elongation, whereas both stimuli are needed for deciliation. Accordingly, in a scratch-wounded epithelium, TGFβ provokes cilium loss exclusively along the wound edge. Increased contractility, a key myofibroblast feature, is necessary and sufficient for deciliation, since constitutively active RhoA, Rac1, or myosin triggers, and down-regulation of myosin or myocardin-related transcription factor prevents, this process. Sustained myosin phosphorylation and consequent deciliation are mediated by a Smad3-, Rac1-, and reactive oxygen species–dependent process. Transitioned myofibroblasts exhibit impaired responsiveness to platelet-derived growth factor-AA and sonic hedgehog, two cilium-associated stimuli. Although the cilium is lost during EMyT, its initial presence contributes to the transition. Thus myofibroblasts represent a unique cilium-less entity with profoundly reprogrammed cilium-related signaling.

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Extracellular matrix-inducing Sox9 orchestrates basal progenitor proliferation and gliogenesis in developing neocortex

10.1101/704890 ◽

2019 ◽

Author(s):

Ayse Güven ◽

Denise Stenzel ◽

Katherine R. Long ◽

Marta Florio ◽

Holger Brandl ◽

...

Keyword(s):

Extracellular Matrix ◽

Cell Fate ◽

Subventricular Zone ◽

Integrin Signaling ◽

Sox9 Expression ◽

Embryonic Mouse ◽

Functional Studies ◽

Basal Progenitor ◽

Developing Neocortex ◽

Stimulation Of

AbstractNeocortex expansion is largely based on the proliferative capacity of basal progenitors (BPs), which is increased by extracellular matrix (ECM) components via integrin signaling. Here we show that Sox9 drives expression of ECM components and that laminin 211 increases BP proliferation in embryonic mouse neocortex. Examination of Sox9 expression reveals that Sox9 is expressed in BPs of developing ferret and human, but not mouse neocortex. Functional studies by conditional Sox9 expression in the mouse BP lineage demonstrate increased BP proliferation, reduced Tbr2 and induction of Olig2 expression, indicative of premature gliogenesis. Conditional Sox9 expression also results in cell non-autonomous stimulation of BP proliferation followed by increased production of upper-layer neurons. Collectively, our findings demonstrate that Sox9 exerts concerted effects on transcription, BP proliferation, neuron production, and neurogenic as well as gliogenic BP cell fate, suggesting that Sox9 acts a master regulator in the subventricular zone to promote neocortical expansion.

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LATS1 but not LATS2 represses autophagy by a kinase-independent scaffold function

Nature Communications ◽

10.1038/s41467-019-13591-7 ◽

2019 ◽

Vol 10 (1) ◽

Cited By ~ 7

Author(s):

Fengyuan Tang ◽

Ruize Gao ◽

Beena Jeevan-Raj ◽

Christof B. Wyss ◽

Ravi K. R. Kalathur ◽

...

Keyword(s):

Therapeutic Strategy ◽

Hippo Pathway ◽

Standard Of Care ◽

Beclin 1 ◽

Hippo Signaling ◽

Hippo Signaling Pathway ◽

Lysine Residues ◽

Core Components ◽

Hcc Cells

AbstractAutophagy perturbation represents an emerging therapeutic strategy in cancer. Although LATS1 and LATS2 kinases, core components of the mammalian Hippo pathway, have been shown to exert tumor suppressive activities, here we report a pro-survival role of LATS1 but not LATS2 in hepatocellular carcinoma (HCC) cells. Specifically, LATS1 restricts lethal autophagy in HCC cells induced by sorafenib, the standard of care for advanced HCC patients. Notably, autophagy regulation by LATS1 is independent of its kinase activity. Instead, LATS1 stabilizes the autophagy core-machinery component Beclin-1 by promoting K27-linked ubiquitination at lysine residues K32 and K263 on Beclin-1. Consequently, ubiquitination of Beclin-1 negatively regulates autophagy by promoting inactive dimer formation of Beclin-1. Our study highlights a functional diversity between LATS1 and LATS2, and uncovers a scaffolding role of LATS1 in mediating a cross-talk between the Hippo signaling pathway and autophagy.

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Abemaciclib induces apoptosis in cardiomyocytes by activating the Hippo signaling pathway

Acta Biochimica et Biophysica Sinica ◽

10.1093/abbs/gmaa066 ◽

2020 ◽

Vol 52 (8) ◽

pp. 875-882

Author(s):

Yajie Zhou ◽

Yanfei Li ◽

Junwei Shen ◽

Jue Li ◽

Xinming Li

Keyword(s):

Signaling Pathway ◽

Quantitative Polymerase Chain Reaction ◽

Cell Counting ◽

Hippo Signaling ◽

Cyclin Dependent Kinase ◽

Cardiac Side Effects ◽

Hippo Signaling Pathway ◽

The Us ◽

Induced Apoptosis

Abstract Abemaciclib is the newest cyclin-dependent kinase 4/6 inhibitor that has received approval from the US Food and Drug Administration for using in patients with advanced breast cancer. However, its potential adverse effects on cardiomyocytes remain unknown. In this study, we used the cell counting kit-8 assay, western blot analysis, flow cytometry, immunostaining, and quantitative polymerase chain reaction to investigate the role of abemaciclib in inducing apoptosis and in inhibiting the viability and proliferation of AC16 human cardiomyocyte cells. The results revealed that abemaciclib induced apoptosis and inhibited cell proliferation by activating the Hippo signaling pathway. This work demonstrates the molecular basis by which abemaciclib induces cardiac side effects, providing a theoretical basis and effective targets for the treatment of cardiac diseases.

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Interaction of the Hippo Pathway and Phosphatases in Tumorigenesis

Cancers ◽

10.3390/cancers12092438 ◽

2020 ◽

Vol 12 (9) ◽

pp. 2438 ◽

Cited By ~ 2

Author(s):

Sahar Sarmasti Emami ◽

Derek Zhang ◽

Xiaolong Yang

Keyword(s):

Signaling Pathway ◽

Hippo Pathway ◽

Underlying Mechanism ◽

Hippo Signaling ◽

Hippo Signaling Pathway ◽

Cellular Processes ◽

Wide Range ◽

Future Direction ◽

The Hippo Pathway

The Hippo pathway is an emerging tumor suppressor signaling pathway involved in a wide range of cellular processes. Dysregulation of different components of the Hippo signaling pathway is associated with a number of diseases including cancer. Therefore, identification of the Hippo pathway regulators and the underlying mechanism of its regulation may be useful to uncover new therapeutics for cancer therapy. The Hippo signaling pathway includes a set of kinases that phosphorylate different proteins in order to phosphorylate and inactivate its main downstream effectors, YAP and TAZ. Thus, modulating phosphorylation and dephosphorylation of the Hippo components by kinases and phosphatases play critical roles in the regulation of the signaling pathway. While information regarding kinase regulation of the Hippo pathway is abundant, the role of phosphatases in regulating this pathway is just beginning to be understood. In this review, we summarize the most recent reports on the interaction of phosphatases and the Hippo pathway in tumorigenesis. We have also introduced challenges in clarifying the role of phosphatases in the Hippo pathway and future direction of crosstalk between phosphatases and the Hippo pathway.

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