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
β-Catenin Signaling Controls Metastasis in Braf-Activated Pten-Deficient Melanomas
William Damsky,William Damsky,David P. Curley,David P. Curley,Manjula Santhanakrishnan,Lara E. Rosenbaum,James T. Platt,Bonnie E. Gould Rothberg,Makoto Mark Taketo,David Dankort,David L. Rimm,Martin McMahon,Marcus Bosenberg +12 more
TL;DR: In this article, β-catenin levels control tumor differentiation and regulate both MAPK/Erk and PI3K/Akt signaling in melanoma, which is a central mediator of melanoma metastasis to lymph nodes and lungs.
Journal ArticleDOI
Genetics of hepatocellular tumors
TL;DR: Comprehensive analyses of genetic alterations have defined two pathways of hepatocarcinogenesis according to the presence or the absence of chromosomal instability: Hepatitis B virus and poorly differentiated tumors are related to chromosome instable tumors associated with frequent TP53 mutations, whereas non-HBV and well-differentiated tumors arerelated to chromosomal stable samples that are frequently β-catenin activated.
Journal ArticleDOI
Antisera induced by infusions of autologous Ad-CD154-leukemia B cells identify ROR1 as an oncofetal antigen and receptor for Wnt5a
Tetsuya Fukuda,Liguang Chen,Tomoyuki Endo,Li Tang,Desheng Lu,Januario E. Castro,George F. Widhopf,Laura Z. Rassenti,Mark J. Cantwell,Charles E. Prussak,Dennis A. Carson,Thomas J. Kipps +11 more
TL;DR: It is concluded that patients with CLL can break immune tolerance to ROR1, which is an oncofetal surface antigen and survival-signaling receptor in this neoplastic disease.
Journal ArticleDOI
Illegitimate WNT signaling promotes proliferation of multiple myeloma cells
Patrick W. B. Derksen,Esther P. M. Tjin,Helen P. Meijer,Melanie D. Klok,Harold D. Mac Gillavry,Marinus H. J. van Oers,Henk M. Lokhorst,Andries C. Bloem,Hans Clevers,Roel Nusse,Ronald van der Neut,Marcel Spaargaren,Steven T. Pals +12 more
TL;DR: It is suggested that multiple myeloma cells are dependent on an active WNT signal, which may have important implications for the management of this incurable form of cancer.
Journal ArticleDOI
Nuclear Overexpression of the Oncoprotein β-Catenin in Colorectal Cancer is Localized Predominantly at the Invasion Front
Thomas Brabletz,Andreas Jung,Kathrin Hermann,Klaus Günther,Werner Hohenberger,Thomas Kirchner +5 more
TL;DR: Using immunohistochemistry, the distribution of overexpressed beta-Catenin within individual colorectal carcinomas was investigated and it was found that surrounding tissue at the invasion front can give signals to the tumor cells, leading to a nuclear translocation of beta- Catenin, where it may play a direct role in tumor invasion processes.