The investigation of the integrative function of focal adhesion kinase (FAK) in human oesophagel squamous cell carcinoma cell lines
Date
2009-04-23T10:14:23Z
Authors
Worsley, Catherine Mary
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Abstract
The expression of focal adhesion kinase (FAK), a non-receptor cytoplasmic tyrosine
kinase, is often upregulated in many cancer types. FAK influences cellular adhesion
and migration, as well as significantly mediating downstream signalling to
components involved in cellular proliferation and survival. Many of these cellular
pathways are facilitated by the interaction of FAK with epidermal growth factor
receptor (EGFR), which is overexpressed in human squamous cell carcinoma. This
cancer type is highly prevalent in South Africa and is characterized by extremely
aggressive clinical behaviour and very poor patient prognosis. The aim of this study
was to investigate FAK expression, localization, and the effects of EGFR activation
on the expression and tyrosine phosphorylation status of FAK in order to shed light
on the migratory behaviour of human oesophageal squamous cell carcinoma. This is
the first study that semi-quantifiably details FAK expression in 5 South African
human oesophageal squamous cell carcinoma cell lines as demonstrated by western
blot analysis. Furthermore, as shown by indirect immunofluorescence, FAK is
localized to focal contacts within migratory structures as well as being abundantly
present within the cytoplasm of the oesophageal squamous cell carcinoma cell lines.
Localization of FAK to the migratory front of these cells may promote focal
adhesion turnover and stimulate cell migration in these cell lines. This study is also
the first demonstration in this cancer type that illustrates the modulation of the expression, cellular localization, proteolytic cleavage and tyrosine phosphorylation
status of FAK by active EGFR. These findings may uncover some of the molecular
mechanisms by which upregulated cell movement influences the metastatic
behaviour of this cancer. Furthermore, the results presented in this study identify
FAK as a key candidate expression, cellular localization, proteolytic cleavage and tyrosine phosphorylation
status of FAK by active EGFR. These findings may uncover some of the molecular
mechanisms by which upregulated cell movement influences the metastatic
behaviour of this cancer. Furthermore, the results presented in this study identify
FAK as a key candidate for anti-cancer therapy in squamous cell carcinoma of the
oesophagus.