Actomyosin contractility modulates Wnt signaling through adherens junction stability

Hall, Eric T.; Hoesing, Elizabeth A.; Sinkovics, Endre; Verheyen, Esther M.

doi:10.1101/220178

Cited by 4 publications

(5 citation statements)

References 55 publications

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“…Accordingly, β-catenin transcriptional activity remained unchanged as evidenced by following by qPCR the expression of the AXIN2 and CCND1 canonical target genes or by TOP/FOP luciferase reporter assay (Figure 5E&F). These results are in agreement with studies showing that increased compression transduced by apical junctions in epithelial cells prevent β-catenin nuclear accumulation 11,16 . Together, these results thus show that the loss of MAGI1 in luminal BCa cells does not promote YAP nor β-catenin signaling, and suggest that these pathways do not mediate the increased tumorigenicity of MAGI1 deficient cells.…”

Section: Resultssupporting

confidence: 93%

MAGI1 inhibits the AMOTL2/p38 stress pathway and prevents luminal breast tumorigenesis

Kantar

Mur

Slaninova

et al. 2020

Preprint

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13Alterations to cell polarization or to intercellular junctions are often associated with epithelial cancer 14 progression, including breast cancers (BCa). We show here that the loss of the junctional scaffold 15 protein MAGI1 is associated with bad prognosis in luminal BCa, and promotes tumorigenesis. E-16 cadherin and the actin binding scaffold AMOTL2 accumulate in MAGI1 deficient cells which are 17 subjected to increased stiffness. These alterations are associated with low YAP activity, the terminal 18 Hippo-pathway effector, but with an elevated ROCK and p38 Stress Activated Protein Kinase activities. 19Blocking ROCK prevented p38 activation, suggesting that MAGI1 limits p38 activity in part through 20 releasing actin strength. Importantly, the increased tumorigenicity of MAGI1 deficient cells is rescued 21 in the absence of AMOTL2 or after inhibition of p38, demonstrating that MAGI1 acts as a tumor-22 suppressor in luminal BCa by inhibiting an AMOTL2/p38 stress pathway. 23

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Section: Resultssupporting

confidence: 93%

MAGI1 inhibits the AMOTL2/p38 stress pathway and prevents luminal breast tumorigenesis

Kantar

Mur

Slaninova

et al. 2020

Preprint

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“…Mechanistically, it was proposed that actomyosin activity at the cell-cell contacts mediates the effect of mechanical forces on Wnt/b-cat signaling (Hall et al, 2017;Hirata et al, 2017). Accordingly, myosin II inhibition with blebbistatin or abolishing the link between E-cadherin and the actin cytoskeleton, via a-cat knockdown, was shown to induce b-cat nuclear accumulation (Hirata et al, 2017).…”

Section: Sensing Mechanical Forces Via Hippo or Yap Signalingmentioning

confidence: 99%

Mechanical Force-Driven Adherens Junction Remodeling and Epithelial Dynamics

2018

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“…Arm has dual roles in disk cells: transducing Wg signals (Hall, Hoesing, Sinkovics, & Verheyen, 2019;Leckband & De Rooij, 2014) and in cell adhesion via AJs, and thus there is a competition for it. Arm has binding sites for adhesion components such as α-catenin, and for transcription control regulators (Bejsovec, 2018).…”

Section: Mechanotransduction In the Diskmentioning

confidence: 99%

“…In addition to actin, the motor protein NMII also acts in the mechanotranduction pathways, NMII generates the contractile force in the CSK and cortex, and increased NMII leads to increased E-Cad activity at the AJs (Hall et al, 2019). The increased E-Cad binds more Arm and actin, which in turn reduces Wg signaling, increases Wts localization, and increases Yki activity.…”

Section: Mechanotransduction In the Diskmentioning

confidence: 99%

Growth control in the Drosophila wing disk

Gou

Stotsky

Othmer

2020

WIREs Mechanisms of Disease

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The regulation of size and shape is a fundamental requirement of biological development and has been a subject of scientific study for centuries, but we still lack an understanding of how organisms know when to stop growing. Imaginal wing disks of the fruit fly Drosophila melanogaster, which are precursors of the adult wings, are an archetypal tissue for studying growth control. The growth of the disks is dependent on many inter‐ and intra‐organ factors such as morphogens, mechanical forces, nutrient levels, and hormones that influence gene expression and cell growth. Extracellular signals are transduced into gene‐control signals via complex signal transduction networks, and since cells typically receive many different signals, a mechanism for integrating the signals is needed. Our understanding of the effect of morphogens on tissue‐level growth regulation via individual pathways has increased significantly in the last half century, but our understanding of how multiple biochemical and mechanical signals are integrated to determine whether or not a cell decides to divide is still rudimentary. Numerous fundamental questions are involved in understanding the decision‐making process, and here we review the major biochemical and mechanical pathways involved in disk development with a view toward providing a basis for beginning to understand how multiple signals can be integrated at the cell level, and how this translates into growth control at the level of the imaginal disk. This article is categorized under: Analytical and Computational Methods > Computational Methods Biological Mechanisms > Cell Signaling Models of Systems Properties and Processes > Cellular Models

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Actomyosin contractility modulates Wnt signaling through adherens junction stability

Abstract: 11Mechanical forces can influence the canonical Wnt signaling pathway in processes like 12 mesoderm differentiation and tissue stiffness during tumorigenesis, but a molecular mechanism 13 involving both in a developing epithelium and its homeostasis is lacking. We identified that

Cited by 4 publications

References 55 publications

MAGI1 inhibits the AMOTL2/p38 stress pathway and prevents luminal breast tumorigenesis

MAGI1 inhibits the AMOTL2/p38 stress pathway and prevents luminal breast tumorigenesis

Mechanical Force-Driven Adherens Junction Remodeling and Epithelial Dynamics

Growth control in the Drosophila wing disk

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