Actomyosin contractility modulates Wnt signaling through adherens junction stability

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.

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Actomyosin contractility modulates Wnt signaling through adherens junction stability

Molecular Biology of the Cell ◽

10.1091/mbc.e18-06-0345 ◽

2019 ◽

Vol 30 (3) ◽

pp. 411-426 ◽

Cited By ~ 5

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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Are We Benign? What Can Wnt Signaling Pathway and Epithelial to Mesenchymal Transition Tell Us about Intracranial Meningioma Progression

Cancers ◽

10.3390/cancers13071633 ◽

2021 ◽

Vol 13 (7) ◽

pp. 1633

Author(s):

Anja Bukovac ◽

Anja Kafka ◽

Marina Raguž ◽

Petar Brlek ◽

Katarina Dragičević ◽

...

Keyword(s):

Wnt Signaling ◽

Signaling Pathway ◽

Epithelial To Mesenchymal Transition ◽

Nuclear Translocation ◽

Active Form ◽

Wnt Signaling Pathway ◽

Future Research ◽

Intracranial Meningioma ◽

Mesenchymal Transition ◽

E Cadherin

Epithelial to mesenchymal transition (EMT), which is characterized by the reduced expression of E-cadherin and increased expression of N-cadherin, plays an important role in the tumor invasion and metastasis. Classical Wnt signaling pathway has a tight link with EMT and it has been shown that nuclear translocation of β-catenin can induce EMT. This research has showed that genes that are involved in cadherin switch, CDH1 and CDH2, play a role in meningioma progression. Increased N-cadherin expression in relation to E-cadherin was recorded. In meningioma, transcription factors SNAIL, SLUG, and TWIST1 demonstrated strong expression in relation to E- and N-cadherin. The expression of SNAIL and SLUG was significantly associated with higher grades (p = 0.001), indicating their role in meningioma progression. Higher grades also recorded an increased expression of total β-catenin followed by an increased expression of its active form (p = 0.000). This research brings the results of genetic and protein analyzes of important molecules that are involved in Wnt and EMT signaling pathways and reveals their role in intracranial meningioma. The results of this study offer guidelines and new markers of progression for future research and reveal new molecular targets of therapeutic interventions.

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