ABSTRACT
Hanahan and Weinberg (2000) described six essential changes to normal cellular function that determine progression to malignancy: ‘self-suffi ciency in growth signals, evasion of programmed cell death, limitless replicative potential, sustained angiogenesis, and tissue invasion and metastasis’. Transmembrane integrin receptor interaction with the extracellular matrix (ECM) stimulates the activation of phosphorylation-dependent signalling cascades that play a critical role in each of these six hallmarks of cancer. Protein phosphorylation creates binding sites that facilitates protein-protein interaction, thereby creating networks of interacting proteins. Kinases catalyse the transfer of the γ-phosphoryl group of ATP to serine, threonine or tyrosine amino acids in the recipient protein. Based on the growing realization that kinases are essential regulators of adhesion-dependent signalling in cancer, they-and their phosphorylated substrates-have become important new targets for treating malignancies and for monitoring activity of chemotherapeutic agents. Th e following sections provide information regarding the phospho-regulation of focal adhesion kinase (FAK), Src, paxillin and p130Cas and discuss how studies of these proteins have led to novel anti-cancer therapies and biomarkers for chemotherapy effi cacy.
