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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A Small Molecule Inhibitor of the β-Catenin-TCF4 Interaction Suppresses Colorectal Cancer Growth In Vitro and In Vivo
Seung-Ho Shin,Do Young Lim,Kanamata Reddy,Margarita Malakhova,Fangfang Liu,Ting Wang,Mengqiu Song,H. S. Chen,Ki Beom Bae,Joohyun Ryu,Kangdong Liu,Mee-Hyun Lee,Ann M. Bode,Zigang Dong +13 more
TL;DR: HI-B1 inhibited β-catenin/TCF4 luciferase activity and preferentially caused apoptosis of cancer cells in which the survival is dependent on β-Catenin, and potentially could be further exploited for biomarker development and therapeutic applications against colon cancer.
Journal ArticleDOI
Fra-1 is a key driver of colon cancer metastasis and a Fra-1 classifier predicts disease-free survival
TL;DR: It is demonstrated that Fra-1 is an important determinant of the metastatic potential of human colon cancer cells, and that theFra-1 classifier can be used as a prognostic predictor in colon cancer patients.
Journal ArticleDOI
Wnt signaling as potential therapeutic target in lung cancer
TL;DR: The results from clinical studies suggest that inhibitors targeting the Wnt pathway show promise against lung cancer, and the regulatory roles of microRNAs in Wnt signaling are expounded, as well as the potential of the WNT pathway to provide biomarkers and therapeutic targets in lung cancer.
Journal ArticleDOI
Emerging role of the β-catenin-PPARγ axis in the pathogenesis of colorectal cancer
Lina Sabatino,Massimo Pancione,Carolina Votino,Tommaso Colangelo,Angelo Lupo,Ettore Novellino,Antonio Lavecchia,Vittorio Colantuoni +7 more
TL;DR: The basic principles are reviewed and new hypotheses underlying the crosstalk between Wnt/β-catenin and PPARγ signaling are presented, which discuss the advances in the understanding as to how their altered regulation can culminate in colon cancer and the efforts aimed at designing novel PParγ agonists endowed with Wnt-Catenin inhibitory effects to be used as therapeutic and/or preventive agents.
Journal ArticleDOI
Wnt signaling pathway: Implications for therapy in lung cancer and bone metastasis
Yongming Xi,Yan Chen +1 more
TL;DR: The aim of this review is to provide a summary regarding the role of the Wnt signaling pathway in lung cancer and bone metastasis, highlighting the aberrant activation of Wnt in this malignancy.
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.