B-catenin expression and associated signalling in moderately differentiated human oesophageal squamous carcinoma cell lines
Year: 2009
Type: dissertation
Abstract: β-catenin links membrane-bound cadherins to the actin cytoskeleton, regulating \ncellular adhesion, and consequently metastasis. Abnormal stabilization of free, \ncytoplasmic β-catenin enhances its transcriptional activities. Factors affecting the \nadhesive and signalling roles of β-catenin may be important in metastatic diseases \nsuch as oesophageal squamous cell carcinoma (SCC). This study focuses on the \nexpression of β-catenin in moderately-differentiated oesophageal SCCs and the \nimpact of three signalling pathways on this. The majority of β-catenin’s \nexpression within moderately-differentiated oesophageal SCCs, under standard in \nvitro conditions, was associated with the plasma membrane, rather than in the \ncytoplasm. This indicates that β-catenin’s role is skewed towards cell-cell \nadhesion, rather than its signalling activities. Lithium, a Wnt pathway mimic, \nelevated cytoplasmic β-catenin concentrations. Membrane concentrations \nsubsequently increased, possibly through E-cadherin sequestration of excess \ncytoplasmic β-catenin. TGF-β1, alone or together with lithium, did not alter β- \ncatenin expression. EGF transiently increased cytoplasmic β-catenin, but did not \nalter total concentration. However, together with lithium, EGF increased \nstabilized cytoplasmic β-catenin concentrations, whilst decreasing membraneassociated \nβ-catenin levels. This indicates that EGF/lithium signals synergistically \nprovoke β-catenin redistribution. This may be induced by posttranslational \nmodification through tyrosine phosphorylation of plasma membrane-associated β- \ncatenin as the concentration of tyrosine, but not serine, phosphorylated β-catenin \nwas increased by these signals. Thus, although the adhesive role of β-catenin \nappears intact, exogenous signals by EGF and lithium can alter, through tyrosine \nphosphorylation, the signalling role of β-catenin whilst reducing its adhesive role \nand thus, may potentiate the metastatic properties of these cells.
Author: Lindsay Jean Gordon McCutcheon
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: green
Funder: National Research Foundation
OpenAlex ID: W2168523475