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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Deregulated PTEN/PI3K/AKT/mTOR signaling in prostate cancer: Still a potential druggable target?
TL;DR: A summary of the biological functions of the major players of this cascade and their deregulation in prostate cancer are provided, summarizing the results of preclinical and clinical studies with PI3K signaling inhibitors and the reasons of failure independent from genomic changes.
Journal ArticleDOI
Wnt Signalling in Acute Myeloid Leukaemia
TL;DR: Targeting Wnt signalling for tumour eradication is an approach that is being explored in haematological and solid tumours, albeit, so far no reliable clinical trial data is available to prove its utility and efficacy.
Journal ArticleDOI
EGFRvIII/integrin β3 interaction in hypoxic and vitronectinenriching microenvironment promote GBM progression and metastasis.
Zhaoyu Liu,Lei Han,Yucui Dong,Yanli Tan,Yongsheng Li,Manli Zhao,Hui Xie,Huanyu Ju,He Wang,Yu Zhao,Qifan Zheng,Qixue Wang,Jun Su,Chuan Fang,Songbin Fu,Tao Jiang,Jiaren Liu,Xia Li,Chunsheng Kang,Huan Ren +19 more
TL;DR: It is demonstrated that EGFRvIII/integrin β3 complexes promote GBM progression and metastasis in the environment of hypoxia and vitronectin-enrichment, and cilengitide may serve as a promising therapeutics for EGFR vIII-positive GBMs.
Journal ArticleDOI
Wnt5a promotes Frizzled-4 signalosome assembly by stabilizing cysteine-rich domain dimerization
Zachary J. DeBruine,Jiyuan Ke,Kaleeckal G. Harikumar,Xin Gu,Peter Borowsky,Bart O. Williams,Wenqing Xu,Laurence J. Miller,H. Eric Xu,Karsten Melcher +9 more
TL;DR: It is suggested that FZD receptors may form signalosomes in response to Wnt binding through the CRDs and that the Wnt palmitoleoyl group is important in promoting these interactions, and a more complete model for Wnt signalosome assembly both intracellularly and at the membrane is provided.
Journal ArticleDOI
Metastasis suppressors in breast cancers: Mechanistic insights and clinical potential
TL;DR: Known metastasis suppressors are cellular factors that, when re-expressed in metastatic cells, functionally inhibit metastasis without significantly inhibiting tumor growth.
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.