Journal ArticleDOI
Wnt3A Induces GSK-3β Phosphorylation and β-Catenin Accumulation Through RhoA/ROCK.
Jae-Gyu Kim,Myoung-Ju Kim,Won-Ji Choi,Mi-Young Moon,Hee-Jun Kim,Jae-Yong Lee,Jaebong Kim,Sung Chan Kim,Seung Goo Kang,Goo-Young Seo,Pyeung-Hyeun Kim,Jae-Bong Park +11 more
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TLDR
The cross‐talk between canonical and non‐canonical signaling pathways of Wnt3A is proposed, which induces GSK‐3β phosphorylation and β‐catenin accumulation through RhoA and ROCK activation.Abstract:
In canonical pathway, Wnt3A has been known to stabilize β-catenin through the dissociation between β-catenin and glycogen synthase kinase-3β (GSK-3β) that suppresses the phosphorylation and degradation of β-catenin. In non-canonical signaling pathway, Wnt was known to activate Rho GTPases and to induce cell migration. The cross-talk between canonical and non-canonical pathways by Wnt signaling; however, has not been fully elucidated. Here, we revealed that Wnt3A induces not only the phosphorylation of GSK-3β and accumulation of β-catenin but also RhoA activation in RAW264.7 and HEK293 cells. Notably, sh-RhoA and Tat-C3 abolished both the phosphorylation of GSK-3β and accumulation of β-catenin. Y27632, an inhibitor of Rho-associated coiled coil kinase (ROCK) and si-ROCK inhibited both GSK-3β phosphorylation and β-catenin accumulation. Furthermore, active domain of ROCK directly phosphorylated the purified recombinant GSK-3β in vitro. In addition, Wnt3A-induced cell proliferation and migration, which were inhibited by Tat-C3 and Y27632. Taken together, we propose the cross-talk between canonical and non-canonical signaling pathways of Wnt3A, which induces GSK-3β phosphorylation and β-catenin accumulation through RhoA and ROCK activation. J. Cell. Physiol. 232: 1104-1113, 2017. © 2016 Wiley Periodicals, Inc.read more
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Molecular mechanism involved in cyclophosphamide-induced cardiotoxicity: Old drug with a new vision
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Regulation of RhoA GTPase and various transcription factors in the RhoA pathway.
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Acute compressive stress activates RHO/ROCK-mediated cellular processes.
Sarah T. Boyle,Jasreen Kular,Max Nobis,Andrew Ruszkiewicz,Paul Timpson,Michael S. Samuel,Michael S. Samuel +6 more
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Cellular Internalization-Induced Aggregation of Porous Silicon Nanoparticles for Ultrasound Imaging and Protein-Mediated Protection of Stem Cells
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TL;DR: It is proposed that the intracellular aggregation of protein drug-loaded TPSi NPs could be a simple but robust strategy for improving the therapeutic effect of stem cell therapy.
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TL;DR: Integrative analyses suggest new markers for aggressive colorectal carcinoma and an important role for MYC-directed transcriptional activation and repression.
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Activation of β-Catenin-Tcf Signaling in Colon Cancer by Mutations in β-Catenin or APC
Patrice J. Morin,Andrew B. Sparks,Vladimir Korinek,Nick Barker,Hans Clevers,Bert Vogelstein,Kenneth W. Kinzler +6 more
TL;DR: Results indicate that regulation of β-catenin is critical to APC's tumor suppressive effect and that this regulation can be circumvented by mutations in either APC or β- catenin.
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Beta-catenin regulates expression of cyclin D1 in colon carcinoma cells.
Osamu Tetsu,Frank McCormick +1 more
TL;DR: It is shown that β-catenin activates transcription from the cyclin D1 promoter, and that sequences within the promoter that are related to consensus TCF/LEF-binding sites are necessary for activation.
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Tumor-associated macrophages: from mechanisms to therapy.
TL;DR: Therapeutic success in targeting these protumoral roles in preclinical models and in early clinical trials suggests that macrophages are attractive targets as part of combination therapy in cancer treatment.
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Rho GTPases: Biochemistry and Biology
Aron B. Jaffe,Alan Hall +1 more
TL;DR: This review presents the best characterized of these biochemical pathways that control some of the most fundamental processes of cell biology common to all eukaryotes, including morphogenesis, polarity, movement, and cell division.