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
More filters
Journal ArticleDOI
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
More filters
Journal ArticleDOI
The effect of non-steroidal anti-inflammatory drugs on human colorectal cancer cells: evidence of different mechanisms of action.
TL;DR: Investigation of the effects of NS-398, indomethacin and aspirin on four human colorectal cancer cell lines found decreased beta-catenin protein expression may mediate the anti-proliferative effects of indometHacin.
Genomic sequencing of colorectal adenocarcinomas identifies a recurrent VTI1A-TCF7L2 fusion
Adam J. Bass,Adam J. Bass,Michael S. Lawrence,Lear E. Brace,Alex H. Ramos,Alex H. Ramos,Yotam Drier,Kristian Cibulskis,Carrie Sougnez,Douglas Voet,Gordon Saksena,Andrey Sivachenko,Rui Jing,Melissa Parkin,Trevor J. Pugh,Trevor J. Pugh,Roel G.W. Verhaak,Nicolas Stransky,Adam T. Boutin,Jordi Barretina,David B. Solit,Evi Vakiani,Wenlin Shao,Yuji Mishina,Markus Warmuth,Jose Jimenez,Derek Y. Chiang,Sabina Signoretti,William G. Kaelin,Nicole Spardy,William C. Hahn,William C. Hahn,Yujin Hoshida,Shuji Ogino,Ronald A. DePinho,Lynda Chin,Levi A. Garraway,Levi A. Garraway,Charles S. Fuchs,Jose Baselga,Jose Baselga,Josep Tabernero,Stacey Gabriel,Eric S. Lander,Eric S. Lander,Gad Getz,Matthew Meyerson,Matthew Meyerson +47 more
TL;DR: In this paper, the authors identify an average of 75 somatic rearrangements per tumor, including complex networks of translocations between pairs of chromosomes, which can lead to essential gene fusions and other oncogenic events.
Journal ArticleDOI
A Monoclonal Antibody against Wnt-1 Induces Apoptosis in Human Cancer Cells
Biao He,Liang You,Kazutsugu Uematsu,Zhidong Xu,Amie Y. Lee,Maria Matsangou,Frank McCormick,David M. Jablons +7 more
TL;DR: It is found that incubation of a monoclonal anti-Wnt-1 antibody induced apoptosis and caused downstream protein changes and induction of apoptosis in human cancer cells, and RNAi targeting of Wnt- 1 in cancer cells overexpressing WNT-1 demonstrated similar downstream proteinChanges.
Journal ArticleDOI
Wnt-5a has tumor suppressor activity in thyroid carcinoma.
TL;DR: Testing the effects of a member of the noncanonical Wnt signaling pathway, Wnt-5a, in primary thyroid carcinomas and in thyroid carcinoma cell lines found that a bell-shaped response was observed with low to undetectable levels in normal tissue and in anaplastic tumors whereas differentiated thyroid carcinomes showed strong positive immunostaining for Wnt -5a.
Journal ArticleDOI
The B-cell tumor-associated antigen ROR1 can be targeted with T cells modified to express a ROR1-specific chimeric antigen receptor.
Michael Hudecek,Michael Hudecek,Thomas M. Schmitt,Sivasubramanian Baskar,Maria Teresa Lupo-Stanghellini,Tetsuya Nishida,Tori N. Yamamoto,Marie Bleakley,Cameron J. Turtle,Cameron J. Turtle,Wen-Chung Chang,Harvey A. Greisman,Brent L. Wood,David G. Maloney,David G. Maloney,Michael C. Jensen,Michael C. Jensen,Christoph Rader,Stanley R. Riddell,Stanley R. Riddell +19 more
TL;DR: A ROR1-specific chimeric antigen receptor was constructed that when expressed in T cells from healthy donors or CLL patients conferred specific recognition of primary B-CLL and mantle cell lymphoma, including rare drug effluxing chemotherapy resistant tumor cells that have been implicated in maintaining the malignancy, but not mature normal B cells.