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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New insights into the mechanisms of epithelial–mesenchymal transition and implications for cancer
TL;DR: It is highlighted how EMT gives rise to a variety of intermediate cell states between the epithelial and the mesenchymal state which could function as cancer stem cells, and its effects on the immunobiology of carcinomas.
Journal ArticleDOI
Wnt signaling in cancer.
TL;DR: Current insights into novel components of Wnt pathways are reviewed and how Wnt signaling affects maintenance of cancer stem cells, metastasis and immune control are described.
Journal ArticleDOI
Cancer stem cells revisited
Eduard Batlle,Hans Clevers +1 more
TL;DR: New developments in the cancer stem cell field are discussed in relationship to changing insights into how normal stem cells maintain healthy tissues and the first successes of therapies based on the CSC concept are emerging.
Journal ArticleDOI
Cdks, cyclins and CKIs: roles beyond cell cycle regulation
TL;DR: The latest revelations about Cdks, cyclins and CKIs are discussed with the goal of showcasing their functional diversity beyond cell cycle regulation and their impact on development and disease in mammals.
Journal ArticleDOI
Mechanisms of Hippo pathway regulation
TL;DR: This review focuses on recent developments in the understanding of the molecular actions of the core Hippo kinase cascade and discusses key open questions in the regulation and function of the Hippo pathway.
References
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Journal ArticleDOI
A genome-wide RNAi screen for Wnt/β-catenin pathway components identifies unexpected roles for TCF transcription factors in cancer
Wei Tang,Michael E. Dodge,Deepika Gundapaneni,C. H. Michnoff,Michael G. Roth,Lawrence G. Lum +5 more
TL;DR: Surprisingly, it is found that the presumed cancer-promoting gene TCF7L2 functions instead as a transcriptional repressor that restricts colorectal cancer (CRC) cell growth.
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The soluble wnt receptor Frizzled8CRD-hFc inhibits the growth of teratocarcinomas in vivo.
TL;DR: This is the first report showing the efficacy of a soluble wnt receptor as an antitumor agent and suggests that further development of wnt antagonists will have utility in treating human cancer.
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Inhibition of tumorigenesis driven by different Wnt proteins requires blockade of distinct ligand-binding regions by LRP6 antibodies
Seth Ettenberg,Olga Charlat,Michael P. Daley,Shanming Liu,Karen Vincent,Darrin Stuart,Alwin Schuller,Jing Yuan,Beatriz Ospina,J. E. F. Green,Qunyan Yu,Renee Walsh,Sharon Li,Rita Schmitz,Holger Heine,Sanela Bilic,Lance Ostrom,Rebecca A. Mosher,K. Felix Hartlepp,Zhenping Zhu,Stephen E. Fawell,Yung-mae Yao,David Raymond Stover,Peter Finan,Jeffery A. Porter,William R. Sellers,Ingo Klagge,Feng Cong +27 more
TL;DR: These studies provide insights into Wnt-induced LRP5/6 activation and show the potential utility of LRP6 antibodies in WNT-driven cancer.
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Human Dkk-1, a gene encoding a Wnt antagonist, responds to DNA damage and its overexpression sensitizes brain tumor cells to apoptosis following alkylation damage of DNA.
TL;DR: Results show that hDkk-1 is a pro-apoptotic gene and suggest that it may play important roles in linking the oncogenic Wnt and p53 tumor suppressor pathways.
Journal ArticleDOI
Identification of SFRP1 as a candidate mediator of stromal-to-epithelial signaling in prostate cancer
Margaret S. Joesting,Steve Perrin,Brian Elenbaas,Stephen E. Fawell,Jeffrey S. Rubin,Omar E. Franco,Simon W. Hayward,Gerald R. Cunha,Paul C. Marker +8 more
TL;DR: Data suggest that overexpression of SFRP1 by prostatic tumor stroma may account for the previously reported capacity of prostatic tumors stroma to provide a pro-proliferative paracrine signal to adjacent epithelial cells.