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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The MITF family of transcription factors: Role in endolysosomal biogenesis, Wnt signaling, and oncogenesis.
TL;DR: How cancers overexpressing MITF, TFEB or TFE3 could rewire the lysosomal pathway, inhibit cellular senescence, and activate Wnt signaling by increasing sequestration of negative regulators of Wnt signaled in multivesicular bodies (MVBs) is reviewed.
Journal ArticleDOI
Green tea polyphenol EGCG suppresses Wnt/β-catenin signaling by promoting GSK-3β- and PP2A-independent β-catenin phosphorylation/degradation
TL;DR: These findings suggest that EGCG exerts its cancer-preventive or anticancer activity against colon cancer cells by promoting the phosphorylation and proteasomal degradation of β-catenin through a mechanism independent of the GSK-3β and PP2A.
Journal ArticleDOI
Identification of the DEAD box RNA helicase DDX3 as a therapeutic target in colorectal cancer.
Marise R. Heerma van Voss,Marise R. Heerma van Voss,Farhad Vesuna,Kari Trumpi,Justin Brilliant,Cynthia A. Berlinicke,Wendy W.J. de Leng,Onno Kranenburg,G. Johan A. Offerhaus,Horst Bürger,Elsken van der Wall,Paul J. van Diest,Venu Raman,Venu Raman +13 more
TL;DR: It is concluded that DDX3 has an oncogenic role in colorectal cancer and inhibition ofDDX3 with the small molecule inhibitor RK-33 causes inhibition of Wnt signaling and may therefore be a promising future treatment strategy for a subset of coloreCTal cancers.
Journal ArticleDOI
A regulatory circuit of miR-125b/miR-20b and Wnt signalling controls glioblastoma phenotypes through FZD6-modulated pathways
Tianzhi Huang,Angel Alvarez,Rajendra P. Pangeni,Craig Horbinski,Songjian Lu,Sung Hak Kim,C. David James,Jeffery J. Raizer,John A. Kessler,Cameron Brenann,Erik P. Sulman,Gaetano Finocchiaro,Ming Tan,Ryo Nishikawa,Xinghua Lu,Ichiro Nakano,Bo Hu,Shi Yuan Cheng +17 more
TL;DR: It is reported that canonical Wnt signalling that is active in proneural (PN) but inactive in mesenchymal (MES) GBM, along withmiR-125b and miR-20b that are expressed at high levels in PN compared with MES, comprise a regulatory circuit that results in inhibition of distinct GBM subtypes.
Journal ArticleDOI
Wnt Signaling in Cancer Metabolism and Immunity
TL;DR: The role of the canonical Wnt/β-catenin pathway in cancer metabolism and immunity is illustrated to explore the potential therapeutic approach of targeting Wnt signaling from a metabolic and immunological perspective.
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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.