B-catenin expression and associated signalling in moderately differentiated human oesophageal squamous carcinoma cell lines

Show simple item record

dc.contributor.author McCutcheon, Lindsay Jean Gordon
dc.date.accessioned 2009-04-01T12:37:14Z
dc.date.available 2009-04-01T12:37:14Z
dc.date.issued 2009-04-01T12:37:14Z
dc.identifier.uri http://hdl.handle.net/10539/6861
dc.description.abstract β-catenin links membrane-bound cadherins to the actin cytoskeleton, regulating cellular adhesion, and consequently metastasis. Abnormal stabilization of free, cytoplasmic β-catenin enhances its transcriptional activities. Factors affecting the adhesive and signalling roles of β-catenin may be important in metastatic diseases such as oesophageal squamous cell carcinoma (SCC). This study focuses on the expression of β-catenin in moderately-differentiated oesophageal SCCs and the impact of three signalling pathways on this. The majority of β-catenin’s expression within moderately-differentiated oesophageal SCCs, under standard in vitro conditions, was associated with the plasma membrane, rather than in the cytoplasm. This indicates that β-catenin’s role is skewed towards cell-cell adhesion, rather than its signalling activities. Lithium, a Wnt pathway mimic, elevated cytoplasmic β-catenin concentrations. Membrane concentrations subsequently increased, possibly through E-cadherin sequestration of excess cytoplasmic β-catenin. TGF-β1, alone or together with lithium, did not alter β- catenin expression. EGF transiently increased cytoplasmic β-catenin, but did not alter total concentration. However, together with lithium, EGF increased stabilized cytoplasmic β-catenin concentrations, whilst decreasing membraneassociated β-catenin levels. This indicates that EGF/lithium signals synergistically provoke β-catenin redistribution. This may be induced by posttranslational modification through tyrosine phosphorylation of plasma membrane-associated β- catenin as the concentration of tyrosine, but not serine, phosphorylated β-catenin was increased by these signals. Thus, although the adhesive role of β-catenin appears intact, exogenous signals by EGF and lithium can alter, through tyrosine phosphorylation, the signalling role of β-catenin whilst reducing its adhesive role and thus, may potentiate the metastatic properties of these cells. en
dc.language.iso en en
dc.title B-catenin expression and associated signalling in moderately differentiated human oesophageal squamous carcinoma cell lines en
dc.type Thesis en

Files in this item

This item appears in the following Collection(s)

Show simple item record

Search WIReDSpace


My Account