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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The mechanisms of genome-wide target gene regulation by TCF7L2 in liver cells
TL;DR: Tcf7l2-silencing enhanced the expression and chromatin occupancy of HNF4α, and co-siRNA experiments revealed that H NF4α was required for the regulation of a subset of metabolic genes by TCF7L2, particularly those involved in lipid and amino-acid metabolism.
Journal ArticleDOI
Divergent Androgen Receptor and Beta-Catenin Signaling in Prostate Cancer Cells.
TL;DR: Evidence is presented that the Wnt/β-catenin pathway might be activated in prostate cancer cells after androgens-deprivation to promote androgen-independent growth, partly through enhanced interaction of β-Catenin with TCF4.
Journal ArticleDOI
Next-generation sequencing-based molecular characterization of primary urinary bladder adenocarcinoma
Somak Roy,Dinesh Pradhan,Wayne L. Ernst,Stephanie Mercurio,Yana G. Najjar,Rahul A. Parikh,Anil V. Parwani,Reetesh K. Pai,Rajiv Dhir,Marina N. Nikiforova +9 more
TL;DR: A striking finding was the distinct lack of genomic alterations across the 51 genes assessed in mucinous subtype of primary bladder adenocarcinoma, suggesting alterations affecting the MAP kinase, PI3K/Akt, Wnt, IDH (metabolic) and Tp53/Rb1 signaling pathways may provide the opportunity for defining targeted therapeutic approaches.
Journal ArticleDOI
Blocking Wnt Secretion Reduces Growth of Hepatocellular Carcinoma Cell Lines Mostly Independent of β-Catenin Signaling
W. Wang,Lei Xu,Pengyu Liu,Kiran Jairam,Yuebang Yin,Kan Chen,Dave Sprengers,Maikel P. Peppelenbosch,Qiuwei Pan,Ron Smits +9 more
TL;DR: Most colorectal and liver cancers with mutations in components of the β-catenin degradation complex do not strongly rely on extracellular Wnt ligand exposure to support optimal growth, and blocking Wnt secretion may aid in tumor suppression through alternative routes currently unappreciated.
Journal ArticleDOI
Breast cancer stem cells: are we ready to go from bench to bedside?
TL;DR: This review will focus on both the challenges and recent advances in the characterization of BCSCs with respect to phenotype, molecular signature and their role in the behaviour of the different molecular subtypes of breast cancer.
References
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Journal ArticleDOI
Comprehensive molecular characterization of human colon and rectal cancer
Donna M. Muzny,Matthew N. Bainbridge,Kyle Chang,Huyen Dinh,Jennifer Drummond,Gerald R. Fowler,Christie Kovar,Lora Lewis,Margaret Morgan,Irene Newsham,Jeffrey G. Reid,Jireh Santibanez,Eve Shinbrot,Lisa R. Trevino,Yuan Qing Wu,Min Wang,Preethi H. Gunaratne,Preethi H. Gunaratne,Lawrence A. Donehower,Chad J. Creighton,David A. Wheeler,Richard A. Gibbs,Michael S. Lawrence,Douglas Voet,Rui Jing,Kristian Cibulskis,Andrey Sivachenko,Andrey Sivachenko,Petar Stojanov,Aaron McKenna,Eric S. Lander,Eric S. Lander,Stacey Gabriel,Li Ding,Robert S. Fulton,Daniel C. Koboldt,Todd Wylie,Jason Walker,David J. Dooling,Lucinda Fulton,Kim D. Delehaunty,Catrina Fronick,Ryan Demeter,Elaine R. Mardis,Richard K. Wilson,Andy Chu,Hye Jung E. Chun,Andrew J. Mungall,Erin Pleasance,A. Gordon Robertson,Dominik Stoll,Miruna Balasundaram,Inanc Birol,Yaron S.N. Butterfield,Eric Chuah,Robin J.N. Coope,Noreen Dhalla,Ranabir Guin,Carrie Hirst,Martin Hirst,Robert A. Holt,Darlene Lee,Haiyan I. Li,Michael Mayo,Richard A. Moore,Jacqueline E. Schein,Jared R. Slobodan,Angela Tam,Nina Thiessen,Richard Varhol,Thomas Zeng,Yongjun Zhao,Steven J.M. Jones,Marco A. Marra,Adam J. Bass,Alex H. Ramos,Gordon Saksena,Andrew D. Cherniack,Stephen E. Schumacher,Barbara Tabak,Scott L. Carter,Nam Pho,Huy V. Nguyen,Robert C. Onofrio,Andrew Crenshaw,Kristin G. Ardlie,Rameen Beroukhim,Wendy Winckler,Matthew Meyerson,Alexei Protopopov,Angela Hadjipanayis,Eunjung Lee,Ruibin Xi,Lixing Yang,Xiaojia Ren,Narayanan Sathiamoorthy,Peng Chieh Chen,Psalm Haseley,Yonghong Xiao,Semin Lee,Jonathan G. Seidman,Lynda Chin,Peter J. Park,Raju Kucherlapati,J. Todd Auman,Katherine A. Hoadley,Ying Du,Matthew D. Wilkerson,Yan Shi,Christina Liquori,Shaowu Meng,Ling Li,Yidi J. Turman,Michael D. Topal,Donghui Tan,Scot Waring,Elizabeth Buda,Jesse Walsh,Corbin D. Jones,Piotr A. Mieczkowski,Darshan Singh,Junyuan Wu,Anisha Gulabani,Peter Dolina,Tom Bodenheimer,Alan P. Hoyle,Janae V. Simons,Matthew G. Soloway,Lisle E. Mose,Stuart R. Jefferys,Saianand Balu,Brian O'Connor,Jan F. Prins,Derek Y. Chiang,D. Neil Hayes,Charles M. Perou,Toshinori Hinoue,Daniel J. Weisenberger,Dennis T. Maglinte,Fei Pan,Benjamin P. Berman,David Van Den Berg,Hui Shen,Timothy J. Triche,Stephen B. Baylin,Peter W. Laird,Gad Getz,Michael S. Noble,Doug Voat,Nils Gehlenborg,Daniel DiCara,Juinhua Zhang,Hailei Zhang,Chang-Jiun Wu,Spring Yingchun Liu,Sachet A. Shukla,Lihua Zhou,Pei Lin,Richard W. Park,Marc Danie Nazaire,James A. Robinson,Helga Thorvaldsdottir,Jill P. Mesirov,Vesteinn Thorsson,Sheila Reynolds,Brady Bernard,Richard Kreisberg,Jake Lin,Lisa Iype,Ryan Bressler,Timo Erkkilä,Madhumati Gundapuneni,Yuexin Liu,Adam Norberg,Thomas Robinson,Da Yang,Wei Zhang,Ilya Shmulevich,Jorma J. de Ronde,Jorma J. de Ronde,Nikolaus Schultz,Ethan Cerami,Giovanni Ciriello,Arthur P. Goldberg,Benjamin Gross,Anders Jacobsen,Jianjiong Gao,Bogumil Kaczkowski,Rileen Sinha,B. Arman Aksoy,Yevgeniy Antipin,Boris Reva,Ronglai Shen,Barry S. Taylor,Marc Ladanyi,Chris Sander,Rehan Akbani,Nianxiang Zhang,Bradley M. Broom,Tod D. Casasent,Anna K. Unruh,Chris Wakefield,Stanley R. Hamilton,R. Craig Cason,Keith A. Baggerly,John N. Weinstein,David Haussler,Christopher C. Benz,Joshua M. Stuart,Stephen C. Benz,J. Zachary Sanborn,Charles J. Vaske,Jingchun Zhu,Christopher Szeto,Gary K. Scott,Christina Yau,Sam Ng,Theodore C. Goldstein,Kyle Ellrott,Eric A. Collisson,Aaron E. Cozen,Daniel R. Zerbino,Christopher Wilks,Brian Craft,Paul T. Spellman,Robert Penny,Troy Shelton,Martha Hatfield,Scott Morris,Peggy Yena,Candace Shelton,Mark Sherman,Joseph Paulauskis,Julie M. Gastier-Foster,Julie M. Gastier-Foster,Jay Bowen,Nilsa C. Ramirez,Nilsa C. Ramirez,Aaron D. Black,Robert E. Pyatt,Robert E. Pyatt,Lisa Wise,Peter White,Peter White,Monica M. Bertagnolli,Jen Brown,Timothy A. Chan,Gerald C. Chu,Christine Czerwinski,Fred Denstman,Rajiv Dhir,Arnulf Dörner,Charles S. Fuchs,Jose G. Guillem,Mary Iacocca,Hartmut Juhl,Andrew Kaufman,Bernard Kohl,Xuan Van Le,Maria C. Mariano,Elizabeth N. Medina,Michael Meyers,Garrett M. Nash,P. Paty,Nicholas J. Petrelli,Brenda Rabeno,William G. Richards,David B. Solit,Pat Swanson,Larissa K. Temple,Joel E. Tepper,Richard Thorp,Efsevia Vakiani,Martin R. Weiser,Joseph Willis,Gary Witkin,Zhaoshi Zeng,Michael J. Zinner,Carsten Zornig,Mark A. Jensen,Robert Sfeir,Ari B. Kahn,Anna L. Chu,Prachi Kothiyal,Zhining Wang,Eric E. Snyder,Joan Pontius,Todd Pihl,Brenda Ayala,Mark Backus,Jessica Walton,Jon Whitmore,Julien Baboud,Dominique L. Berton,Matthew C. Nicholls,Deepak Srinivasan,Rohini Raman,Stanley Girshik,Peter A. Kigonya,Shelley Alonso,Rashmi N. Sanbhadti,Sean P. Barletta,John M. Greene,David Pot,Kenna R. Mills Shaw,Laura A.L. Dillon,Kenneth H. Buetow,Tanja Davidsen,John A. Demchok,Greg Eley,Martin L. Ferguson,Peter Fielding,Carl F. Schaefer,Margi Sheth,Liming Yang,Mark S. Guyer,Bradley A. Ozenberger,Jacqueline D. Palchik,Jane Peterson,Heidi J. Sofia,Elizabeth J. Thomson +320 more
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.