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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Leukemia stem cells in T-ALL require active Hif1α and Wnt signaling
Vincenzo Giambra,Catherine E. Jenkins,Sonya H Lam,Catherine Hoofd,Miriam Belmonte,Xuehai Wang,Sam Gusscott,Deanne Gracias,Andrew P. Weng +8 more
TL;DR: It is reported that active Wnt signaling is restricted to minor subpopulations within bulk tumors, that these Wnt-active subsets are highly enriched for leukemia-initiating cells (LICs), and that genetic inactivation of β-catenin severely reduces LIC frequency.
Journal ArticleDOI
Iron deprivation in cancer--potential therapeutic implications.
TL;DR: Iron homeostasis in non-malignant and malignant cells, the widespread effects of iron depletion on the cell, the various iron chelators that have been explored in the treatment of cancer, and the tumor types that have be most commonly studied in the context of iron chelation are reviewed.
Journal ArticleDOI
Comprehensive Characterization of Alternative Polyadenylation in Human Cancer.
Yu Xiang,Youqiong Ye,Yanyan Lou,Yang Yang,Chunyan Cai,Zhao Zhang,Tingting Mills,Ning Yuan Chen,Yoonjin Kim,Fatma Muge Ozguc,Lixia Diao,Harry Karmouty-Quintana,Yang Xia,Rodney E. Kellems,Zheng Chen,Michael R. Blackburn,Seung Hee Yoo,Ann-Bin Shyu,Gordon B. Mills,Leng Han +19 more
TL;DR: This study revealed a striking global 3'UTR shortening in cancer cell lines compared with tumor samples and suggested PABPN1 as the master regulator in regulating APA profile across different cancer types, and showed that APA events could affect drug sensitivity, especially of drugs targeting chromatin modifiers.
Journal ArticleDOI
Dynamics of Mechanosensitive Neural Stem Cell Differentiation.
TL;DR: Investigating adult neural stem cell (NSC) fate commitment using an oligonucleotide‐crosslinked ECM platform that for the first time offers dynamic and reversible control of stiffness reveals that ECM stiffness dictates NSC lineage commitment by signaling via a YAP and β‐catenin interaction during a defined temporal window.
Journal ArticleDOI
Autocrine WNT2 signaling in fibroblasts promotes colorectal cancer progression
Nina Kramer,J Schmöllerl,Christine Unger,Harini Nivarthi,Albin Rudisch,Daniela Unterleuthner,Martin Scherzer,Angelika Riedl,Matthias Artaker,Ilija Crncec,D Lenhardt,Thomas Schwarz,B Prieler,Xiaonan Han,Markus Hengstschläger,Julia Schüler,Robert Eferl,Richard Moriggl,Wolfgang Sommergruber,Helmut Dolznig +19 more
TL;DR: It is shown for the first time that WNT2 is one of the most significantly induced genes in CRC stroma as compared to normal stroma, and W NT2 and its receptor are classifies as promising stromal targets to confine cancer progression in combination with conventional or targeted therapies.
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.