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...

The beginning of mesodermal development involves the aggregation of newly gastrulated cells into epithelial fields, as a prelude to organ formation. To analyze the molecular regulation of this initial patterning, we have focused on the Wnt family of secreted signaling proteins, molecules which have been shown to promote embryonic patterning by regulating cell-cell associations. In this study, w...

Wnt proteins represent a family of secreted, lipid-modified glycoproteins that can activate different intracellular pathways. Upon binding to certain members of the Frizzled family of Wnt receptors some Wnts like Wnt-4, Wnt-5A or Wnt-11 are able to elicit an intracellular release of calcium ions. This calcium signaling acitivity is sufficient to activate calcium sensitive enzymes like protein k...

The cranial bones and dermis differentiate from mesenchyme beneath the surface ectoderm. Fate selection in cranial mesenchyme requires the canonical Wnt effector molecule β-catenin, but the relative contribution of Wnt ligand sources in this process remains unknown. Here we show Wnt ligands are expressed in cranial surface ectoderm and underlying supraorbital mesenchyme during dermal and osteob...

The proto-oncogene Wnt-1 plays an essential role in fetal brain development and causes hyperplasia and tumorigenesis when activated ectopically in the mouse mammary gland. When expressed in certain mammary epithelial cell lines, the gene causes morphological transformation and excess cell proliferation at confluence. Like other members of the mammalian Wnt family, Wnt-1 encodes secretory glycop...

Interactions between developmental signaling pathways govern the formation and function of stem cells. Prostaglandin (PG) E2 regulates vertebrate hematopoietic stem cells (HSC). Similarly, the Wnt signaling pathway controls HSC self-renewal and bone marrow repopulation. Here, we show that wnt reporter activity in zebrafish HSCs is responsive to PGE2 modulation, demonstrating a direct interactio...

BACKGROUND Canonical and non-canonical Wnt signaling pathways modulate diverse cellular processes during embryogenesis and post-natally. Their deregulations have been implicated in cancer development and progression. Wnt signaling is essential for odontogenesis. The ameloblastoma is an odontogenic epithelial neoplasm of enamel organ origin. Altered expressions of Wnts-1, -2, -5a, and -10a are d...