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
Citations
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Therapeutic strategies against cancer stem cells in human colorectal cancer.
TL;DR: The discovery of cancer stem cells has resulted in the definition of novel therapeutic targets and the development of novel experimental therapies for CRC, however, further investigations are required in order to apply these novel drugs in human CRC.
Journal ArticleDOI
In vivo Wnt pathway inhibition of human squamous cell carcinoma growth and metastasis in the chick chorioallantoic model
Shannon F. Rudy,Shannon F. Rudy,J. Chad Brenner,Jennifer L. Harris,Jun Liu,Jianwei Che,Megan V. Scott,Megan V. Scott,John H. Owen,Christine M. Komarck,Martin P. Graham,Emily Bellile,Carol R. Bradford,Mark E. Prince,Thomas E. Carey +14 more
TL;DR: The data demonstrate decreased tumor growth and metastases in tumors from cell lines that showed in vitro responses to WNT974, providing evidence that this agent may have a role in future HNSCC therapy.
Journal ArticleDOI
Functional and genomic analyses reveal therapeutic potential of targeting β-catenin/CBP activity in head and neck cancer.
Vinay K. Kartha,Khalid Alamoud,Khikmet Sadykov,Bach-Cuc Nguyen,Fabrice Laroche,Hui Feng,Jin-A Lee,Sara I. Pai,Xaralabos Varelas,Ann Marie Egloff,Jennifer E. Snyder-Cappione,Anna C. Belkina,Manish V. Bais,Stefano Monti,Maria A. Kukuruzinska +14 more
TL;DR: Results identify β-catenin/CBP interaction as a novel target for anti-HNSCC therapy and provide evidence that derivatives of ICG-001 with enhanced inhibitory activity may serve as an effective strategy to interfere with aggressive features of HNSCC.
Journal ArticleDOI
SLC6A14, a Na+/Cl--coupled amino acid transporter, functions as a tumor promoter in colon and is a target for Wnt signaling.
Mohd. Omar Faruk Sikder,Sathish Sivaprakasam,Timothy P. Brown,Muthusamy Thangaraju,Yangzom D. Bhutia,Vadivel Ganapathy +5 more
TL;DR: It is shown that SLC6A14 is essential for colon cancer and that its up-regulation involves, at least partly, Wnt signaling, and that it is identified as a promising drug target for the treatment of colon cancer.
Journal ArticleDOI
Decreased expression of Dkk1 and Dkk3 in human clear cell renal cell carcinoma
TL;DR: A significant decrease in the Dkk1 and Dkk3 mRNA and protein levels in the tumor tissues compared with the adjacent normal tissues revealed may present a novel molecular target for the diagnosis and therapeutic treatment of ccRCC.
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.