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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Kdm2a/b Lysine Demethylases Regulate Canonical Wnt Signaling by Modulating the Stability of Nuclear β-Catenin
TL;DR: It is shown that, upon Wnt activation, the stability of nuclear β-catenin is regulated via methylation/demethylation, which is required for controlling the output of the Wnt/β- catenin signaling pathway to maintain normal cellular functions.
Journal ArticleDOI
Let-7 inhibits self-renewal of hepatocellular cancer stem-like cells through regulating the epithelial-mesenchymal transition and the Wnt signaling pathway
TL;DR: Let-7 miRNAs, especially let-7a, will be a promising therapeutic strategy in the treatment of HCC through eliminating HCC stem cells, which could be achieved by their inhibitory effect on the Wnt signaling pathway.
Journal ArticleDOI
Wnt and Notch signaling govern self-renewal and differentiation in a subset of human glioblastoma stem cells.
Nishani Rajakulendran,Katherine J. Rowland,Hayden J. Selvadurai,Moloud Ahmadi,Nicole I. Park,Sergey Naumenko,Sonam Dolma,Ryan J Ward,Milly So,Lilian Lee,Graham MacLeod,Clarissa C. Pasiliao,Caroline Brandon,Ian D. Clarke,Michael D. Cusimano,Mark Bernstein,Nizar N. Batada,Stephane Angers,Peter B. Dirks +18 more
TL;DR: The role of Wnt/βcatenin signaling in GBM stem cell renewal and fate decisions is investigated and new contexts for Wnt modulation for targeting stem cell differentiation and self-renewal in G BM heterogeneity are identified.
Journal ArticleDOI
Wnt/β-catenin signaling in bone marrow niche
TL;DR: The ability to modulate the Wnt pathway either positively or negatively may be of therapeutic relevance, and the controlled activation of Wnt signaling might allow us to enhance stem and progenitor cell activity when regeneration is needed.
Journal ArticleDOI
Wnt Signaling in Cell Motility and Invasion: Drawing Parallels between Development and Cancer
TL;DR: Recent findings and analogies between Wnt signaling in developmental processes and tumor progression are discussed, with a particular focus on cell motility and matrix invasion and the roles of the ARF (ADP-Ribosylation Factor) and Rho-family small GTP-binding proteins are highlighted.
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.