The investigation of the integrative function of focal adhesion kinase (FAK) in human oesophagel squamous cell carcinoma cell lines

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.