STAT3 paradoxically stimulates β-catenin expression but inhibits β-catenin function.
Bottom Line: Firstly, we investigated biochemical interaction by inhibiting STAT3 and β-catenin (through gene knock-down and dominant-negative TCF4 expression) in nine CRC cell lines. β-catenin inhibition did not affect STAT3 levels, whereas STAT3 knock-down resulted in reduced β-catenin mRNA and protein levels.The reduction in β-catenin protein was not prevented by proteasome inhibition, and IL6-induced STAT3 activation resulted in increased β-catenin mRNA.We conclude that STAT3 regulates β-catenin but β-catenin does not regulate STAT3.
Affiliation: Academic Unit of Molecular Pathology, Nottingham University, Nottingham, UK.Show MeSH
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Mentions: The immunohistochemical expression of STAT3 and β-catenin was tested in a small series of primary CRCs. Staining for β-catenin was seen in all compartments (i.e. membranous, cytoplasmic and nuclear), whilst STAT3 staining was seen only in the cytoplasm and nuclei. The mean score for all assessable cores from each individual case was used in analysis. For analysis of cytoplasmic staining (of both proteins), the median score was used as a cut-off point to dichotomize into ‘positive’ and ‘negative’. For nuclear staining for STAT3, the median score was used as the cut-off whilst, for β-catenin, any nuclear staining was scored as positive. There was a positive association between nuclear STAT3 expression and nuclear β-catenin expression (P = 0.022, Table 1, Figures 2 and S2).
Affiliation: Academic Unit of Molecular Pathology, Nottingham University, Nottingham, UK.