figure with caption
Upon stabilization of cytoplasmic β-catenin by Wnt signaling or oncogenic activation, β-catenin translocates to the nucleus, where it induces transcriptional events via its association with TCF/LEF transcription factors.
caption
May be Daxx involved?
iHOP Daxx
Epigenetic dysregulation of secreted Frizzled-related proteins in multiple myeloma. 2009
In addition, we identified new mechanisms for Frzb antitumor activities. Frzb reduced c-Met expression and inhibited Met-mediated signaling, associated with up-regulation of epithelial markers (i.e., keratins 8 and 18) and down-regulation of mesenchymal markers (i.e., vimentin, N-cadherin, fibronectin, Slug, and Twist). Similar to Frzb, silencing of c-Met by short hairpin RNA or using a dominant-negative LRP5 receptor also suppressed Met signaling, leading to reduced cellular motility, invasion, and in vivo tumor growth. Given recent studies indicating an important role of c-Met in sarcoma development and progression, our data showed that Frzb expression was significantly inversely correlated with Met expression in both STS cell lines and tissues. These results suggested the usefulness of Frzb in modulating Met signaling as a new treatment strategy for STS.
Frzb, a secreted Wnt antagonist, decreases growth and invasiveness of fibrosarcoma cells associated with inhibition of Met signaling. 2008
A clinically relevant model of osteoinduction: a process requiring calcium phosphate and BMP/Wnt signaling. 2009
c-met and CD44
Selective suppression of CD44 in keratinocytes of mice bearing an antisense CD44 transgene driven by a tissue-specific promoter disrupts hyaluronate metabolism in the skin and impairs keratinocyte proliferation.1997
CD44 is a type I transmembrane protein and functions as the major cellular adhesion molecule for hyaluronic acid, a component of the extracellular matrix. CD44 is expressed in most human cell types
Jpn J Cancer Res. 1999 May;90(5):485-9.
Silencing of the CD44 gene by CpG methylation in a human gastric carcinoma cell line., 1999
We analyzed 8 human gastric carcinoma cell lines for the expression of CD44 by northern blot analysis and reverse transcription-polymerase chain reaction (RT-PCR), and identified 1 cell line MKN-28 that did not express CD44. In an attempt to clarify the mechanism responsible for the inactivation of CD44 gene expression in this cell line, we investigated the methylation status around the promoter region of CD44 gene by digestion of the DNA with the methylation-sensitive restriction enzyme HpaII. The promoter region of CD44 in MKN-28 revealed hypermethylation, whereas other CD44-positive cell lines did not. Furthermore, treatment of MKN-28 with the demethylating agent 5-azacytidine restored the expression of the gene. These results suggest that CD44 expression is controlled by a DNA hypermethylation mechanism in MKN-28.
