xct790 has been researched along with Neoplasms* in 2 studies
2 other study(ies) available for xct790 and Neoplasms
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WNT11 expression is induced by estrogen-related receptor alpha and beta-catenin and acts in an autocrine manner to increase cancer cell migration.
Elevated expression of the orphan nuclear receptor estrogen-related receptor α (ERRα) has been associated with a negative outcome in several cancers, although the mechanism(s) by which this receptor influences the pathophysiology of this disease and how its activity is regulated remain unknown. Using a chemical biology approach, it was determined that compounds, previously shown to inhibit canonical Wnt signaling, also inhibited the transcriptional activity of ERRα. The significance of this association was revealed in a series of biochemical and genetic experiments that show that (a) ERRα, β-catenin (β-cat), and lymphoid enhancer-binding factor-1 form macromolecular complexes in cells, (b) ERRα transcriptional activity is enhanced by β-cat expression and vice versa, and (c) there is a high level of overlap among genes previously shown to be regulated by ERRα or β-cat. Furthermore, silencing of ERRα and β-cat expression individually or together dramatically reduced the migratory capacity of breast, prostate, and colon cancer cells in vitro. This increased migration could be attributed to the ERRα/β-cat-dependent induction of WNT11. Specifically, using (a) conditioned medium from cells overexpressing recombinant WNT11 or (b) WNT11 neutralizing antibodies, we were able to show that this protein was the key mediator of the promigratory activities of ERRα/β-cat. Together, these data provide evidence for an autocrine regulatory loop involving transcriptional upregulation of WNT11 by ERRα and β-cat that influences the migratory capacity of cancer cells. Topics: Autocrine Communication; beta Catenin; Blotting, Western; Cadherins; Cell Line, Tumor; Cell Movement; Cell Survival; ERRalpha Estrogen-Related Receptor; Gene Expression Regulation, Neoplastic; HCT116 Cells; Heat-Shock Proteins; Humans; MSX1 Transcription Factor; Neoplasms; Nitriles; Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; Receptors, Estrogen; Reverse Transcriptase Polymerase Chain Reaction; RNA Interference; Signal Transduction; Thiazoles; Transcription Factors; Transcriptional Activation; Wnt Proteins | 2010 |
Modulating estrogen receptor-related receptor-alpha activity inhibits cell proliferation.
High expression of the estrogen receptor-related receptor (ERR)-alpha in human tumors is correlated to a poor prognosis, suggesting an involvement of the receptor in cell proliferation. In this study, we show that a synthetic compound (XCT790) that modulates the activity of ERRalpha reduces the proliferation of various cell lines and blocks the G(1)/S transition of the cell cycle in an ERRalpha-dependent manner. XCT790 induces, in a p53-independent manner, the expression of the cell cycle inhibitor p21(waf/cip)(1) at the protein, mRNA, and promoter level, leading to an accumulation of hypophosphorylated Rb. Finally, XCT790 reduces cell tumorigenicity in Nude mice. Topics: Animals; Cell Cycle; Cell Line, Tumor; Cell Proliferation; Down-Regulation; ERRalpha Estrogen-Related Receptor; Gene Expression Regulation, Neoplastic; Humans; Mice; Neoplasms; Nitriles; Receptors, Estrogen; Thiazoles | 2009 |