Novel synthetic antagonists of canonical Wnt signaling inhibit colorectal cancer cell growth

Cancer Research
Jo WaalerStefan Krauss


Canonical Wnt signaling is deregulated in several types of human cancer where it plays a central role in tumor cell growth and progression. Here we report the identification of 2 new small molecules that specifically inhibit canonical Wnt pathway at the level of the destruction complex. Specificity was verified in various cellular reporter systems, a Xenopus double-axis formation assay and a gene expression profile analysis. In human colorectal cancer (CRC) cells, the new compounds JW67 and JW74 rapidly reduced active β-catenin with a subsequent downregulation of Wnt target genes, including AXIN2, SP5, and NKD1. Notably, AXIN2 protein levels were strongly increased after compound exposure. Long-term treatment with JW74 inhibited the growth of tumor cells in both a mouse xenograft model of CRC and in Apc(Min) mice (multiple intestinal neoplasia, Min). Our findings rationalize further preclinical and clinical evaluation of these new compounds as novel modalities for cancer treatment.


Aug 6, 1996·Proceedings of the National Academy of Sciences of the United States of America·P S Klein, D A Melton
Mar 29, 2000·Proceedings of the National Academy of Sciences of the United States of America·A J RowanI P Tomlinson
Mar 27, 2001·Annual Review of Pharmacology and Toxicology·C J Phiel, P S Klein
Apr 18, 2003·Current Biology : CB·Michael T VeemanRandall T Moon
Jan 30, 2004·Cancer Cell·Maina LepourceletRamesh A Shivdasani
Jul 17, 2004·Cancer Research·Julien MazieresDavid M Jablons
Aug 18, 2004·Proceedings of the National Academy of Sciences of the United States of America·Katayoon H EmamiMichael Kahn
Jan 27, 2005·Biochemical and Biophysical Research Communications·Chi Hoon ParkChul Hak Yang
Nov 23, 2005·Biochemistry·Jufang ShanJie Zheng
Dec 2, 2006·Nature Reviews. Drug Discovery·Nick Barker, Hans Clevers
Jan 9, 2007·Current Opinion in Genetics & Development·Paul Polakis
Apr 25, 2007·Proceedings of the National Academy of Sciences of the United States of America·Kumar SukhdeoDaniel R Carrasco
Jan 8, 2008·Cancer Science·Miki ShitashigeTesshi Yamada
Mar 19, 2008·Molecular Cancer Therapeutics·Shlomo Handeli, Julian A Simon
Mar 12, 2009·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Giovanni AlmanzarArya Biragyn
Sep 18, 2009·Nature·Shih-Min A HuangFeng Cong
Oct 5, 2010·Nature Chemical Biology·Curtis A ThorneEthan Lee


Mar 12, 2013·Journal of Medicinal Chemistry·Andrew VoronkovStefan Krauss
Dec 4, 2013·Journal of Medicinal Chemistry·Zihao HuaErin F Dimauro
Sep 29, 2012·Current Pharmaceutical Design·Andrey Voronkov, Stefan Krauss
May 14, 2014·Seminars in Cancer Biology·Cara JamiesonBeric R Henderson
Aug 9, 2011·Annual Review of Pharmacology and Toxicology·Feng CongShih-Min A Huang
May 5, 2012·FEBS Letters·Tatjana HolzerDietmar Gradl
Nov 7, 2014·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Adele AlagiaRamon Eritja
Aug 14, 2015·International Journal of Molecular Sciences·Sai-Sai TangXing-Dong Xiong
Feb 19, 2014·Fertility and Sterility·Masanori OnoSerdar E Bulun
Dec 17, 2015·Future Medicinal Chemistry·Shilong ZhengGuangdi Wang
Feb 24, 2015·Developmental Biology·Laura J A Hardwick, Anna Philpott
Feb 11, 2012·EMBO Reports·Michel V HadjihannasJürgen Behrens
May 8, 2013·The FEBS Journal·Lari LehtiöStefan Krauss
May 24, 2012·The EMBO Journal·Paul Polakis
Nov 20, 2015·Cell Death & Disease·L KongY Li
Jun 20, 2013·Evidence-based Complementary and Alternative Medicine : ECAM·Jar-Yi HoCheng-Ping Yu
Apr 9, 2015·Nature Reviews. Clinical Oncology·Naoko TakebeS Percy Ivy
Mar 24, 2015·Trends in Pharmacological Sciences·Delphine SéhédicEmmanuel Garcion
Oct 10, 2014·European Journal of Medicinal Chemistry·Paride LiscioEmidio Camaioni
May 11, 2016·European Journal of Medicinal Chemistry·Amit NathubhaiMichael D Threadgill
Feb 26, 2016·Blood·Ashujit TagdeDonald Kufe
Apr 8, 2015·PloS One·Sylvie MaubantThierry Dubois
Aug 3, 2016·PloS One·Nina Marie PedersenHarald Stenmark
Jan 15, 2014·Experimental Biology and Medicine·Joshua K RobertsonTerence J Van Raay
Apr 4, 2017·Gastroenterology·Chang-Kyung KimVincent W Yang
Apr 4, 2017·Basic & Clinical Pharmacology & Toxicology·Tor Espen Thorvaldsen
May 20, 2017·Nutrition and Cancer·Majid Tafrihi, Roohollah Nakhaei Sistani
Jun 2, 2017·British Journal of Pharmacology·Dustin J FlanaganToby J Phesse
Oct 27, 2017·Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine·Xiong JinHyunggee Kim
Sep 15, 2017·British Journal of Pharmacology·Laura MariottiSebastian Guettler
Jun 18, 2017·Genes & Development·Daichao XuJunying Yuan
Dec 17, 2017·Pharmacological Reviews·Sébastien FoulquierW Matthijs Blankesteijn
Nov 7, 2019·Cells·Muhammad HaseebSangdun Choi
Aug 21, 2015·American Journal of Physiology. Cell Physiology·Laura NovellasdemuntVivian S W Li
Sep 16, 2011·Journal of Separation Science·Kristin O SvendsenSteven Ray Wilson
Apr 9, 2013·Expert Review of Anticancer Therapy·Daniel Klotz
Sep 26, 2018·Scientific Reports·Lorenzo M FernandesFrank A Simmen
Dec 13, 2018·Frontiers in Physiology·Laura J A Hardwick, Anna Philpott
Nov 14, 2018·Biochemical Society Transactions·Luca Palazzo, Ivan Ahel
Apr 10, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Bo LiLiang Chen
Sep 12, 2014·Molecular BioSystems·Peng ZhanXinyong Liu
Apr 18, 2017·Current Colorectal Cancer Reports·Emma M SchatoffLukas E Dow
Jul 10, 2017·Journal of Molecular Neuroscience : MN·Alexandre ValléeJean-Noël Vallée
Apr 21, 2017·Medical Oncology·Shaoyun ChenHuanwen Tang
Jan 19, 2019·Scientific Reports·Malini MenonChristopher J Lord
Dec 4, 2019·Molecular Pharmacology·Zheng Zhong, David M Virshup
Dec 7, 2017·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Xiong JinHyunggee Kim
Jul 1, 2015·Molecular Cancer Research : MCR·Tor Espen ThorvaldsenHarald Stenmark

Related Concepts

Cell Division Phases
Colorectal Neoplasms
Signal Transduction
Cell Line, Tumor
Wnt Proteins
Malignant Neoplasms
Cell Growth

Trending Feeds


Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Synthetic Genetic Array Analysis

Synthetic genetic arrays allow the systematic examination of genetic interactions. Here is the latest research focusing on synthetic genetic arrays and their analyses.

Congenital Hyperinsulinism

Congenital hyperinsulinism is caused by genetic mutations resulting in excess insulin secretion from beta cells of the pancreas. Here is the latest research.

Neural Activity: Imaging

Imaging of neural activity in vivo has developed rapidly recently with the advancement of fluorescence microscopy, including new applications using miniaturized microscopes (miniscopes). This feed follows the progress in this growing field.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Epigenetic Memory

Epigenetic memory refers to the heritable genetic changes that are not explained by the DNA sequence. Find the latest research on epigenetic memory here.

Cell Atlas of the Human Eye

Constructing a cell atlas of the human eye will require transcriptomic and histologic analysis over the lifespan. This understanding will aid in the study of development and disease. Find the latest research pertaining to the Cell Atlas of the Human Eye here.

Femoral Neoplasms

Femoral Neoplasms are bone tumors that arise in the femur. Discover the latest research on femoral neoplasms here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.