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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Targeting Wnt Signaling for Gastrointestinal Cancer Therapy: Present and Evolving Views.
TL;DR: An overview of current clinical trials to target Wnt signaling, with a major focus on gastrointestinal cancers, is provided and the caveats and alternative strategies for therapeutically targeting Wnt signalling for cancer treatment are discussed.
Journal ArticleDOI
Postnatal ablation of osteoblast Smad4 enhances proliferative responses to canonical Wnt signaling through interactions with β-catenin.
Valerie S Salazar,Nicholas Zarkadis,Lisa Huang,Marcus Watkins,Jacqueline Kading,Sheri L. Bonar,Jin Norris,Gabriel Mbalaviele,Roberto Civitelli +8 more
TL;DR: It is proposed that Smad4 and Tcf/Lef transcription complexes compete for &bgr;-catenin, thus restraining cWnt-dependent proliferative signals while favoring the matrix synthesizing activity of osteoblasts.
Journal ArticleDOI
E7386, a Selective Inhibitor of the Interaction between β-Catenin and CBP, Exerts Antitumor Activity in Tumor Models with Activated Canonical Wnt Signaling.
Kazuhiko Yamada,Yusaku Hori,Satoshi Inoue,Yuji Yamamoto,Kentaro Iso,Hiroshi Kamiyama,Atsumi Yamaguchi,Takayuki Kimura,Mai Uesugi,Junichi Ito,Masahiro Matsuki,Kazutaka Nakamoto,Hitoshi Harada,Naoki Yoneda,Atsushi Takemura,Ikuo Kushida,Naomi Wakayama,Kenji Kubara,Yu Kato,Taro Semba,Akira Yokoi,Masayuki Matsukura,Takenao Odagami,Masao Iwata,Akihiko Tsuruoka,Toshimitsu Uenaka,Junji Matsui,Tomohiro Matsushima,Kenichi Nomoto,Hiroyuki Kouji,Takashi Owa,Yasuhiro Funahashi,Yoichi Ozawa +32 more
TL;DR: In this article, an orally active selective inhibitor of the interaction between β-catenin and CREB binding protein, which is part of the Wnt/β-Catenin signaling pathway, was presented.
Journal Article
Inhibiting CREPT reduces the proliferation and migration of non-small cell lung cancer cells by down-regulating cell cycle related protein.
Tao Liu,Weimiao Li,Wuping Wang,Ying Sun,Yunfeng Ni,Hao Xing,Jinghua Xia,Xuejiao Wang,Zhipei Zhang,Xiaofei Li +9 more
TL;DR: It is proposed that CREPT may promote NSCLC cell growth and migration through the c-myc and CDC25A signaling molecules.
Journal ArticleDOI
Genomic differences between black and white patients implicate a distinct immune response to papillary renal cell carcinoma
David J. Paulucci,John P. Sfakianos,Anders Jacobsen Skanderup,Kathleen Kan,Che-Kai Tsao,Matthew D. Galsky,A. Ari Hakimi,Ketan K. Badani +7 more
TL;DR: Findings suggest that race may have implications for distinct immune responses to cancer and that the use of immunotherapies, and VEGFR inhibitors to target these pathways may improve survival in black patients with advanced pRCC.
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.