Wnt signaling is dysregulated in many cancers and is therefore an attractive therapeutic target. The focus of drug development has recently shifted away from downstream inhibitors of β-catenin. Active inhibitors of Wnt secretion and Wnt/receptor interactions have been developed that are now entering clinical trials. Such agents include inhibitors of Wnt secretion, as well as recombinant protein...

The pervasive influence of secreted Wnt signaling proteins in tissue homeostasis and tumorigenesis has galvanized efforts to identify small molecules that target Wnt-mediated cellular responses. By screening a diverse synthetic chemical library, we have discovered two new classes of small molecules that disrupt Wnt pathway responses; whereas one class inhibits the activity of Porcupine, a membr...

WNT signaling pathway is implicated in carcinogenesis, embryogenesis and organogenesis [4]. WNTs are a family of secreted-type glycoproteins with 22∼24 conserved cysteine residues. WNT signals are transduced through seven-transmembrane-type WNT receptors encoded by Frizzled (FZD) genes to the β-catenin TCF pathway, the JNK pathway, or the Ca2+-releasing pathway. Gain-of-function mutations of po...

Wnt/β-catenin signalling directs fundamental processes during metazoan development and can be aberrantly activated in cancer. Wnt stimulation induces the recruitment of the scaffold protein Axin from an inhibitory destruction complex to a stimulatory signalosome. Here we analyse the early effects of Wnt on Axin and find that the ADP-ribose polymerase Tankyrase (Tnks)--known to target Axin for p...

Wnt/β-catenin signalling plays essential roles in embryonic development as well as tissue homoeostasis in adults. Thus abnormal regulation of Wnt/β-catenin signalling is linked to a variety of human diseases, including cancer, osteoporosis and Alzheimer's disease. Owing to the importance of Wnt signalling in a wide range of biological fields, a better understanding of its precise mechanisms cou...

Similarly to the Wnt protein palmitoyltransferase, porcupine (PPN) is essential to the activation of the Wnt/β-catenin signaling pathway. However, little is known about the role of PPN activity in human gastric cancer, one of the most common causes of cancer-related mortality. Real-time quantitative PCR was used to detect the expression levels of PPN in paired gastric cancer tissues. Cell proli...

Wnt and Shh signaling pathways are critical for the development and maturation of many epithelial tissues. Both pathways have roles in stem cell maintenance, tissue development, and tumorigenesis. However, linkage between these pathways in mammalian systems had not been well established. Here, we report that Shh expression in fungiform papillae and formation of normal mature fungiform papillae ...

Activation of the Wnt/beta-catenin signaling pathway has been associated with human cancers. To test whether Wnt-2 signal is a survival factor in human melanoma cells and thus represents a potential therapeutic target, we investigated the effects of inhibition of Wnt-2 signaling in human melanoma cell lines. We have developed a novel monoclonal antibody against the NH(2) terminus of the human W...

The importance of the Wnt signaling cascade in the fields of developmental biology, regenerative medicine, cancer genetics, and neurobiology has fueled a wide search for potent pharmacological agents capable of controlling Wnt signaling. Numerous fields of study have lent assistance to this endeavor, yielding both natural and synthetic compounds that are capable of inducing or inhibiting Wnt at...

Regulation of Wnt signaling is crucial for embryonic development and adult homeostasis. Here we study the role of Syndecan-4 (SDC4), a cell-surface heparan sulphate proteoglycan, and Fibronectin (FN), in Wnt/β-catenin signaling. Gain- and loss-of-function experiments in mammalian cell lines and Xenopus embryos demonstrate that SDC4 and FN inhibit Wnt/β-catenin signaling. Epistatic and biochemic...