scholarly journals Wnt Signaling Induces Asymmetric Dynamics in the Actomyosin Cortex of the C. elegans Endomesodermal Precursor Cell

2021 ◽  
Vol 9 ◽  
Author(s):  
Francesca Caroti ◽  
Wim Thiels ◽  
Michiel Vanslambrouck ◽  
Rob Jelier
Keyword(s):  
Wnt Signaling ◽  
Wnt Signaling Pathway ◽  
Spherical Shape ◽  
Precursor Cell ◽  
Cell Cortex ◽  
Asymmetric Distribution ◽  
Cell Stage ◽  
Cortical Tension ◽  
Daughter Cells ◽  
E Cadherin

During asymmetrical division of the endomesodermal precursor cell EMS, a cortical flow arises, and the daughter cells, endodermal precursor E and mesodermal precursor MS, have an enduring difference in the levels of F-actin and non-muscular myosin. Ablation of the cell cortex suggests that these observed differences lead to differences in cortical tension. The higher F-actin and myosin levels in the MS daughter coincide with cell shape changes and relatively lower tension, indicating a soft, actively moving cell, whereas the lower signal in the E daughter cell is associated with higher tension and a more rigid, spherical shape. The cortical flow is under control of the Wnt signaling pathway. Perturbing the pathway removes the asymmetry arising during EMS division and induces subtle defects in the cellular movements at the eight-cell stage. The perturbed cellular movement appears to be associated with an asymmetric distribution of E-cadherin across the EMS cytokinesis groove. ABpl forms a lamellipodium which preferentially adheres to MS by the E-cadherin HMR-1. The HMR-1 asymmetry across the groove is complete just at the moment cytokinesis completes. Perturbing Wnt signaling equalizes the HMR-1 distribution across the lamellipodium. We conclude that Wnt signaling induces a cortical flow during EMS division, which results in a transition in the cortical contractile network for the daughter cells, as well as an asymmetric distribution of E-cadherin.

RUNX1-ETO Stimulates Wnt Signaling by Inhibiting the Function of ETO Family Member Proteins.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 2554-2554
Author(s):  
Amy Moore ◽  
Emilios Tahinci ◽  
Ethan Lee ◽  
Scott Hiebert
Keyword(s):  
Fusion Protein ◽  
Wnt Signaling ◽  
Family Member ◽  
Wnt Signaling Pathway ◽  
Tumor Formation ◽  
Myelogenous Leukemia ◽  
Cell Stage ◽  
Expression Of Genes ◽  
Transcriptional Corepressors

Abstract The t(8;21) is one of the most frequent chromosomal translocations associated with acute myelogenous leukemia (AML). This translocation generates a fusion protein, RUNX1-ETO, consisting of the N-terminus of RUNX1 fused to a nearly full-length ETO protein. The RUNX1-ETO fusion protein stimulates the expression of genes that are regulated by Wnt signaling. The Wnt signaling pathway plays a key role in embryonic development and aberrations to this pathway are frequently involved in tumor formation. Therefore, we sought to define the molecular mechanism by which RUNX1-ETO may stimulate Wnt signaling. We have demonstrated that the ETO family member, Mtgr1, functions as a corepressor for TCF4 and that the levels of the TCF-regulated gene, c-Myc, are upregulated in Mtgr1-null mice. Here we show that the Xenopus homolog of Mtgr1, XETOR, can impair Wnt signaling and induce ventralization in a Xenopus axis duplication assay, a classical assay used to define the hierarchy of components in the Wnt pathway. Specifically, microinjection of in vitro transcribed XETOR mRNA was performed in the marginal zone of both dorsal blastomeres at the 2 to 4 cell stage with increasing amounts of XETOR. Embryos were monitored through stage 26. Compared to control embryos, the embryos injected with XETOR mRNA were ventralized and failed to develop head structures. Conversely, although each of the ETO family member proteins associated with TCF4, RUNX1-ETO failed to bind to TCF4 in co-immunoprecipitation experiments. Mtgr1 was originally identified as a RUNX1-ETO-associated protein. Therefore, we tested whether the fusion protein impairs the action of Mtgr1 as a co-repressor for TCF4. RUNX1-ETO associated with Mtgr1, and Mtgr1 failed to associate with TCF4 when RUNX1-ETO was co-expressed. Thus, RUNX1-ETO appears to stimulate TCF-dependent transcription by interfering with the action of the ETO family of transcriptional corepressors.

scholarly journals Frequent accumulation of nuclear E-cadherin and alterations in the Wnt signaling pathway in esophageal squamous cell carcinomas

2007 ◽  
Vol 21 (3) ◽  
pp. 271-281 ◽  
Author(s):  
Sima Salahshor ◽  
Richard Naidoo ◽  
Stefano Serra ◽  
Warren Shih ◽  
Ming-Sound Tsao ◽  
...  
Keyword(s):  
Wnt Signaling ◽  
Signaling Pathway ◽  
Squamous Cell ◽  
Wnt Signaling Pathway ◽  
Squamous Cell Carcinomas ◽  
Esophageal Squamous Cell Carcinomas ◽  
E Cadherin

scholarly journals A Daple-Akt feed-forward loop enhances noncanonical Wnt signals by compartmentalizing β-catenin

2017 ◽  
Vol 28 (25) ◽  
pp. 3709-3723 ◽  
Author(s):  
Nicolas Aznar ◽  
Nina Sun ◽  
Ying Dunkel ◽  
Jason Ear ◽  
Matthew D. Buschman ◽  
...  
Keyword(s):  
Wnt Signaling ◽  
Cross Talk ◽  
Cellular Proliferation ◽  
Wnt Signaling Pathway ◽  
Colony Growth ◽  
Cell Contact ◽  
Long Distance ◽  
Canonical Wnt ◽  
The Impact ◽  
E Cadherin

Cellular proliferation is antagonistically regulated by canonical and noncanonical Wnt signals; their dysbalance triggers cancers. We previously showed that a multimodular signal transducer, Daple, enhances PI3-K→Akt signals within the noncanonical Wnt signaling pathway and antagonistically inhibits canonical Wnt responses. Here we demonstrate that the PI3-K→Akt pathway serves as a positive feedback loop that further enhances noncanonical Wnt signals by compartmentalizing β-catenin. By phosphorylating the phosphoinositide- (PI) binding domain of Daple, Akt abolishes Daple’s ability to bind PI3-P-enriched endosomes that engage dynein motor complex for long-distance trafficking of β-catenin/E-cadherin complexes to pericentriolar recycling endosomes (PCREs). Phosphorylation compartmentalizes Daple/β-catenin/E-cadherin complexes to cell–cell contact sites, enhances noncanonical Wnt signals, and thereby suppresses colony growth. Dephosphorylation compartmentalizes β-catenin on PCREs, a specialized compartment for prolonged unopposed canonical Wnt signaling, and enhances colony growth. Cancer-associated Daple mutants that are insensitive to Akt mimic a constitutively dephosphorylated state. This work not only identifies Daple as a platform for cross-talk between Akt and the noncanonical Wnt pathway but also reveals the impact of such cross-talk on tumor cell phenotypes that are critical for cancer initiation and progression.

scholarly journals Effects of microRNA-136 on melanoma cell proliferation, apoptosis, and epithelial–mesenchymal transition by targetting PMEL through the Wnt signaling pathway

2017 ◽  
Vol 37 (5) ◽  
Author(s):  
Jiu-Jiang Wang ◽  
Zhi-Feng Li ◽  
Xiao-Jing Li ◽  
Zhao Han ◽  
Ling Zhang ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Wnt Signaling ◽  
Signaling Pathway ◽  
Melanoma Cell ◽  
Epithelial Mesenchymal Transition ◽  
Wnt Signaling Pathway ◽  
Melanoma Cells ◽  
Model Group ◽  
Mesenchymal Transition ◽  
E Cadherin

The study aims to evaluate the effects of miR-136 on the proliferation, apoptosis, and epithelial–mesenchymal transition (EMT) of melanoma cells by targetting premelanosome protein (PMEL) through the Wnt signaling pathway. After establishment of melanoma mouse models, melanoma (model group) and normal tissues (normal group) were collected. Immunohistochemistry was performed to determine PMEL protein concentration. Mouse melanoma cells were assigned into control, blank, negative control (NC), miR-136 mimics, miR-136 inhibitors, siRNA-PMEL, and miR-136 inhibitors + siRNA-PMEL, LiC1 (Wnt signaling pathway activator), and siRNA-PMEL+ LiCl groups. MTT, Scratch test, Transwell assay, and flow cytometry were performed to measure cell proliferation, migration, invasion, and apoptosis. Quantitative real-time PCR (qRT-PCR) and Western blotting were performed to evaluate miR-136, PMEL, β-catenin, Wnt3a, Bcl-2, Bax, Caspase, E-cadherin, and N-cadherin expressions. PMEL is highly expressed in melanoma tissues. MiR-136, Bax, Caspase, and E-cadherin expressions decreased in the model group, whereas PMEL, β-catenin, Bcl-2, Wnt3a, and N-cadherin expressions increased. Bax, Caspase, and E-cadherin expressions increased in the miR-136 mimics and siRNA-PMEL groups, whereas the expressions decreased in the miR-136 inhibitors group and LiC1 group. PMEL, β-catenin, Bcl-2, Wnt3a, and N-cadherin expressions, cell proliferation, migration, and invasion decreased, and the apoptosis rate inceased in the miR-136 mimics and siRNA-PMEL groups; whereas the tendencies were opposite to those in the miR-136 inhibitors group and LiC1 group. In the siRNA-PMEL+ LiCl group, PMEL expression decreased. These findings indicated that overexpression of miR-136 inhibits melanoma cell EMT, proliferation, migration, invasion, and promotes apoptosis by targetting PMEL through down-regulation of the Wnt signaling pathway.

scholarly journals Tension-dependent stabilization of E-cadherin limits cell-cell contact expansion

2020 ◽  
Author(s):  
Jana Slováková ◽  
Mateusz Sikora ◽  
Silvia Caballero-Mancebo ◽  
S.F. Gabriel Krens ◽  
Walter A. Kaufmann ◽  
...  
Keyword(s):  
Threshold Level ◽  
Critical Threshold ◽  
Cell Cortex ◽  
Cell Contact ◽  
Total Size ◽  
Cortical Tension ◽  
Pulling Forces ◽  
Contact Size ◽  
E Cadherin ◽  
Cell Cell

AbstractTension of the actomyosin cell cortex plays a key role in determining cell-cell contact growth and size. The level of cortical tension outside of the cell-cell contact, when pulling at the contact edge, scales with the total size to which a cell-cell contact can grow1,2. Here we show in zebrafish primary germ layer progenitor cells that this monotonic relationship only applies to a narrow range of cortical tension increase, and that above a critical threshold, contact size inversely scales with cortical tension. This switch from cortical tension increasing to decreasing progenitor cell-cell contact size is caused by cortical tension promoting E-cadherin anchoring to the actomyosin cytoskeleton, thereby increasing clustering and stability of E-cadherin at the contact. Once tension-mediated E-cadherin stabilization at the contact exceeds a critical threshold level, the rate by which the contact expands in response to pulling forces from the cortex sharply drops, leading to smaller contacts at physiologically relevant timescales of contact formation. Thus, the activity of cortical tension in expanding cell-cell contact size is limited by tension stabilizing E-cadherin-actin complexes at the contact.

PAR-2 is asymmetrically distributed and promotes association of P granules and PAR-1 with the cortex in C. elegans embryos

Development ◽  
1996 ◽  
Vol 122 (10) ◽  
pp. 3075-3084 ◽  
Author(s):  
L. Boyd ◽  
S. Guo ◽  
D. Levitan ◽  
D.T. Stinchcomb ◽  
K.J. Kemphues
Keyword(s):  
Cell Cycle ◽  
Germ Line ◽  
Cell Cortex ◽  
Asymmetric Distribution ◽  
Cell Stage ◽  
Posterior Cortex ◽  
P Granules ◽  
C Elegans ◽  
Cortical Localization ◽  
The One

The par genes participate in the process of establishing cellular asymmetries during the first cell cycle of Caenorhabditis elegans development. The par-2 gene is required for the unequal first cleavage and for asymmetries in cell cycle length and spindle orientation in the two resulting daughter cells. We have found that the PAR-2 protein is present in adult gonads and early embryos. In gonads, the protein is uniformly distributed at the cell cortex, and this subcellular localization depends on microfilaments. In the one-cell embryo, PAR-2 is localized to the posterior cortex and is partitioned into the posterior daughter, P1, at the first cleavage. PAR-2 exhibits a similar asymmetric cortical localization in P1, P2, and P3, the asymmetrically dividing blastomeres of germ line lineage. This distribution in embryos is very similar to that of PAR-1 protein. By analyzing the distribution of the PAR-2 protein in various par mutant backgrounds we found that proper asymmetric distribution of PAR-2 depends upon par-3 activity but not upon par-1 or par-4. par-2 activity is required for proper cortical localization of PAR-1 and this effect requires wild-type par-3 gene activity. We also find that, although par-2 activity is not required for posterior localization of P granules at the one-cell stage, it is required for proper cortical association of P granules in P1.

scholarly journals Actomyosin contractility modulates Wnt signaling through adherens junction stability

2017 ◽  
Author(s):  
Eric T. Hall ◽  
Elizabeth Hoesing ◽  
Endre Sinkovics ◽  
Esther M. Verheyen
Keyword(s):  
Wnt Signaling ◽  
Gene Transcription ◽  
Target Gene ◽  
Nuclear Translocation ◽  
Adherens Junctions ◽  
Wnt Signaling Pathway ◽  
Epithelial Tissue ◽  
Actomyosin Contractility ◽  
Target Gene Transcription ◽  
E Cadherin

AbstractMechanical forces can influence the canonical Wnt signaling pathway in processes like mesoderm differentiation and tissue stiffness during tumorigenesis, but a molecular mechanism involving both in a developing epithelium and its homeostasis is lacking. We identified that increased non-muscle myosin II activation and cellular contraction inhibited Wnt target gene transcription in developing Drosophila. Genetic interactions studies identified this effect was due to myosin-induced accumulation of cortical F-actin resulting in clustering and accumulation of E-cadherin to the adherens junctions. E-cadherin titrates any available β-catenin, the Wnt pathway transcriptional co-activator, to the adherens junctions in order to maintain cell-cell adhesion under contraction. We show that decreased levels of cytoplasmic β-catenin result in insufficient nuclear translocation for full Wnt target gene transcription. Our work elucidates a mechanism in which the dynamic activation of actomyosin contractility refines patterning of Wnt transcription during development and maintenance of epithelial tissue in organisms.

scholarly journals E-Cadherin/β-Catenin Complex and the Epithelial Barrier

2011 ◽  
Vol 2011 ◽  
pp. 1-6 ◽  
Author(s):  
Xinrui Tian ◽  
Zhuola Liu ◽  
Bo Niu ◽  
Jianlin Zhang ◽  
Thian Kui Tan ◽  
...  
Keyword(s):  
Wnt Signaling ◽  
Signaling Pathway ◽  
Epithelial Mesenchymal Transition ◽  
Wnt Signaling Pathway ◽  
Epithelial Barrier ◽  
Aberrant Expression ◽  
Mesenchymal Transition ◽  
A Cell ◽  
Suppressive Action ◽  
E Cadherin

E-Cadherin/β-catenin complex plays an important role in maintaining epithelial integrity and disrupting this complex affect not only the adhesive repertoire of a cell, but also the Wnt-signaling pathway. Aberrant expression of the complex is associated with a wide variety of human malignancies and disorders of fibrosis resulting from epithelial-mesenchymal transition. These associations provide insights into the complexity that is likely responsible for the fibrosis/tumor suppressive action of E-cadherin/β-catenin.

scholarly journals Actomyosin contractility modulates Wnt signaling through adherens junction stability

2019 ◽  
Vol 30 (3) ◽  
pp. 411-426 ◽  
Author(s):  
Eric T. Hall ◽  
Elizabeth Hoesing ◽  
Endre Sinkovics ◽  
Esther M. Verheyen
Keyword(s):  
Wnt Signaling ◽  
Gene Transcription ◽  
Target Gene ◽  
Nuclear Translocation ◽  
Adherens Junctions ◽  
Wnt Signaling Pathway ◽  
Epithelial Tissue ◽  
Actomyosin Contractility ◽  
Target Gene Transcription ◽  
E Cadherin

Actomyosin contractility can influence the canonical Wnt signaling pathway in processes like mesoderm differentiation and tissue stiffness during tumorigenesis. We identified that increased nonmuscle myosin II activation and cellular contraction inhibited Wnt target gene transcription in developing Drosophila imaginal disks. Genetic interactions studies were used to show that this effect was due to myosin-induced accumulation of cortical F-actin resulting in clustering and accumulation of E-cadherin to the adherens junctions. This results in E-cadherin titrating any available β-catenin, the Wnt pathway transcriptional coactivator, to the adherens junctions in order to maintain cell–cell adhesion under contraction. We show that decreased levels of cytoplasmic β-catenin result in insufficient nuclear translocation for full Wnt target gene transcription. Previous studies have identified some of these interactions, but we present a thorough analysis using the wing disk epithelium to show the consequences of modulating myosin phosphatase. Our work elucidates a mechanism in which the dynamic promotion of actomyosin contractility refines patterning of Wnt transcription during development and maintenance of epithelial tissue in organisms.

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