Src family tyrosine kinases (SFKs) are overexpressed and activated in variety of human tumours including colon, breast and pancreatic cancers. In particular, SFK activity is increased in greater than 80% of colon tumours and this can serve as an independent negative prognostic indicator for disease progression and patient survival.
SFKs are known to be important for a range of fundamental cellular responses including cell cycle progression and cell adhesion. In cancer, such processes are derailed and SFK activation is associated with several aspects of the transformed phenotype including increased proliferation, migration and invasion.
Our recent studies have identified SFKs as substrates for the protein tyrosine phosphatase TCPTP. Our preliminary results indicate that TCPTP may regulate SFKs during G1 progression and in response to integrin ligation. Thus, TCPTP may be important for SFK contributions to cellular proliferation, adhesion and migration.
In this proposal we will determine whether TCPTP is important for the regulation of SFKs in cancer. We will explore TCPTP's potential to modulate SFK-mediated tumourigenicity and assess whether loss of TCPTP may enhance SFK signalling in tumours.
This project explores the molecular basis for tumour formation and may lead to the identification of novel diagnostics or treatment approaches.