The highly conserved wnt gene family has roles in developmental processes ranging from axis formation to cell fate determination. The polychaete Platynereis dumerilii has retained 12 of the 13 ancient wnt subfamilies and is a good model system to study the roles of the wnt ligands in spiralian development. While it has been shown that Platynereis uses a global beta-catenin-mediated binary cell ...

The wingless (Wnt) signaling is suggested as a fundamental hierarchical pathway in regulation of proliferation and differentiation of cells. The Wnt ligands are small proteins of about 40 kDa essentially for regulation and initiation of the Wnt activity. They are secreted proteins requiring acylation for activity in the Wnt signaling cascade and for functional interactivity with transmembrane p...

Convincing evidence has accumulated to identify the Frizzled proteins as receptors for the Wnt growth factors. In parallel, a number of secreted frizzled-like proteins with a conserved N-terminal frizzled motif have been identified. One of these proteins, Frzb-1, binds Wnt-1 and Xwnt-8 proteins and antagonizes Xwnt-8 signaling in Xenopus embryos. Here we report that Frzb-1 blocks Wnt-1 induced ...

Regulation of Wnt transcriptional targets is thought to occur by a transcriptional switch. In the absence of Wnt signaling, sequence-specific DNA-binding proteins of the TCF family repress Wnt target genes. Upon Wnt stimulation, stabilized beta-catenin binds to TCFs, converting them into transcriptional activators. C-terminal-binding protein (CtBP) is a transcriptional corepressor that has been...

The Wnt signaling pathway must be properly modulated to ensure an appropriate output: pathological conditions result from either insufficient or excessive levels of Wnt signal. For example, hyperactivation of the Wnt pathway is associated with various cancers and subnormal Wnt signaling can lead to increased invasiveness of tumor cells. We found that the Caenorhabditis elegans ortholog of the F...

Wnt ligands are secreted glycoproteins controlling gene expression and cytoskeleton reorganization involved in embryonic development of the nervous system. However, their role in later stages of brain development, particularly in the regulation of established synaptic connections, is not known. We found that Wnt-5a acutely and specifically upregulates synaptic NMDAR currents in rat hippocampal ...

Oligodendrocyte precursor cells (OPCs) are generated from multiple progenitor domains in the telencephalon in developmental succession from ventral to dorsal. Previous studies showed that Wnt signaling inhibits the differentiation of OPCs into mature oligodendrocytes. Here we explored the hypothesis that Wnt signaling limits the generation of OPCs from neural progenitors during forebrain develo...

NSC67657 is a new steroid drug that induces monocytic differentiation of acute myeloid leukemia cells. Here, we demonstrate that NSC67657 has opposing effects on expression of downstream targets of inhibitor of β-catenin and TCF (ICAT) and Wnt signaling in HL60 cells. ICAT binds to β-catenin, and this interaction is further increased in NSC67657-differentiated cells. ICAT overexpression decreas...

Aberrant regulation of the Wnt signaling pathway is a prevalent theme in cancer biology. From the earliest observation that Wnt overexpression could lead to malignant transformation of mouse mammary tissue to the most recent genetic discoveries gleaned from tumor genome sequencing, the Wnt pathway continues to evolve as a central mechanism in cancer biology. This article summarizes the evidence...

Purpose: Hepatocellular carcinoma (HCC) is a heterogeneous cancer with active Wnt signaling. Underlying biologic mechanisms remain unclear and no drug targeting this pathway has been approved todate.Weaimed to characterizeWnt-pathway aberrations inHCCpatients, and to investigate sorafenib as a potential Wnt modulator in experimental models of liver cancer. Experimental Design: The Wnt-pathway w...