B-catenin expression and associated signalling in moderately differentiated human oesophageal squamous carcinoma cell lines
Date
2009-04-01T12:37:14Z
Authors
McCutcheon, Lindsay Jean Gordon
Journal Title
Journal ISSN
Volume Title
Publisher
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.