Journal ArticleDOI
WNT signalling pathways as therapeutic targets in cancer
Jamie N. Anastas,Randall T. Moon +1 more
TLDR
This work has shown that WNTs and their downstream effectors regulate various processes that are important for cancer progression, including tumour initiation, tumour growth, cell senescence, cell death, differentiation and metastasis, and improved drug-discovery platforms and new technologies have facilitated the discovery of agents that can alter WNT signalling in preclinical models.Abstract:
Since the initial discovery of the oncogenic activity of WNT1 in mouse mammary glands, our appreciation for the complex roles for WNT signalling pathways in cancer has increased dramatically. WNTs and their downstream effectors regulate various processes that are important for cancer progression, including tumour initiation, tumour growth, cell senescence, cell death, differentiation and metastasis. Although WNT signalling pathways have been difficult to target, improved drug-discovery platforms and new technologies have facilitated the discovery of agents that can alter WNT signalling in preclinical models, thus setting the stage for clinical trials in humans.read more
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Tyrosine-based signal mediates LRP6 receptor endocytosis and desensitization of Wnt/β-catenin pathway signaling.
TL;DR: The results reveal molecular mechanisms by which LRP6 endocytosis routes regulate its phosphorylation and the strength of Wnt/β-catenin signaling, and have implications on how this pathway can be modulated in human diseases.
Journal ArticleDOI
Demyelination in Multiple Sclerosis: Reprogramming Energy Metabolism and Potential PPARγ Agonist Treatment Approaches
TL;DR: PPARγ agonists interfere with reprogramming energy metabolism by directly inhibiting the WNT/β-catenin pathway and circadian rhythms and could appear as promising treatments in MS due to these interactions.
Journal ArticleDOI
Regulation of influenza virus replication by Wnt/β-catenin signaling.
Sunil More,Xiaoyun Yang,Zhengyu Zhu,Gayan Bamunuarachchi,Yujie Guo,Chaoqun Huang,Keith Bailey,Jordan P. Metcalf,Lin Liu +8 more
TL;DR: The intraperitoneal administration of iCRT14 reduced viral load, improved clinical signs, and partially protected mice from influenza virus infection.
Journal ArticleDOI
The Wnt Signaling Antagonist Dapper1 Accelerates Dishevelled2 Degradation via Promoting Its Ubiquitination and Aggregate-induced Autophagy.
TL;DR: The findings suggest that Dpr1 promotes the ubiquitination of Dvl2 by pVHL and mediates the protein aggregate-elicited autophagy initiation, which shows that protein aggregates can induceAutophagy to facilitate their clearance.
Journal ArticleDOI
Sam68 Allows Selective Targeting of Human Cancer Stem Cells
Yannick D. Benoit,Ryan R. Mitchell,Ruth M. Risueño,Luca Orlando,Borko Tanasijevic,Allison L. Boyd,Lili Aslostovar,Kyle R. Salci,Zoya Shapovalova,Jennifer Russell,Masakatsu Eguchi,Diana Golubeva,Monica Graham,Anargyros Xenocostas,Michael Trus,Ronan Foley,Brian Leber,Tony J. Collins,Mickie Bhatia +18 more
TL;DR: Using the ICG-001 and CWP family of small molecules, Sam68 is revealed as a previously unappreciated modulator of Wnt/β-catenin signaling within CSCs that alters Wnt signaling toward apoptosis and differentiation induction.
References
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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.
Journal ArticleDOI
Lessons from Hereditary Colorectal Cancer
TL;DR: The authors are grateful to the members of their laboratories for their contributions to the reviewed studies and to F. Giardiello and S. Hamilton for photographs of colorectal lesions.
Journal ArticleDOI
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.
Journal ArticleDOI
Complex networks orchestrate epithelial–mesenchymal transitions
TL;DR: Understanding how mesenchymal cells arise from an epithelial default status will also have a strong impact in unravelling the mechanisms that control fibrosis and cancer progression.
Journal ArticleDOI
Constitutive Transcriptional Activation by a β-Catenin-Tcf Complex in APC−/− Colon Carcinoma
Vladimir Korinek,Nick Barker,Patrice J. Morin,Dick F. van Wichen,Roel A. de Weger,Kenneth W. Kinzler,Bert Vogelstein,Hans Clevers +7 more
TL;DR: Constitutive transcription of Tcf target genes, caused by loss of APC function, may be a crucial event in the early transformation of colonic epithelium.