Src in cancer: deregulation and consequences for cell behaviour.
Considerable evidence now implicates elevated expression and/or activity of Src in cancer development. In cells, endogenous Src is switched from an inactive to an active state by a variety of mechanisms that simultaneously relieve constraints on the kinase and protein-interacting Src homology (SH) domains. As a result, Src is translocated to the cell periphery, often to sites of cell adhesion, where myristylation mediates attachment to the inner surface of the plasma membrane. From these peripheral sites, Src's catalytic activity initiates intracellular signal transduction pathways that influence cell growth and adhesion strength, the latter contributing to control of cell migration. De-regulation in cancer cells may therefore enhance tumour growth and/or stimulate migratory or invasive potential in cells that would normally be relatively non-motile. Evidence now exists to suggest that Src may also influence the life or death decisions that cells make during many biological processes. Thus, Src modulation in cancer cells can alter cell responses that are often perturbed in cancer. Consequently, there is optimism that drugs which inhibit Src's kinase activity, or the activity of its downstream effectors, might have profound effects on cancer cell behaviour and be useful therapeutic agents.
Frame
Margaret C
MC
The Beatson Institute for Cancer Research and Institute of Biomedical and Life Sciences, CRC Beatson Laboratories (University of Glasgow), Glasgow, UK. gpma67@udcf.gla.ac.uk
D000818:Animals; D002455:Cell Division; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D002470:Cell Survival; D015195:Drug Design; D004789:Enzyme Activation; D004847:Epithelial Cells / Q000201:enzymology; D020555:GTP-Binding Protein Regulators / Q000502:physiology; D015972:Gene Expression Regulation, Neoplastic; D016391:Genes, src; D006801:Humans; D008958:Models, Molecular; D009369:Neoplasms / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D015398:Signal Transduction; D013379:Substrate Specificity; D019061:src-Family Kinases / Q000235:genetics / Q000378:metabolism / Q000502:physiology*
D020555:GTP-Binding Protein Regulators; D019061:src-Family Kinases