title: Metastasis promoter S100A4 is a potentially valuable molecular target for cancer therapy.
abstract: The growth, invasion and metastatic spread of cancer have been identified with the deregulation of cell proliferation, altered intercellular and cell-substratum adhesion and enhanced motility and the deposition of disseminated cancer cells at distant sites. The identification of therapeutic targets for cancer is crucial to human welfare. Drug development, molecular modelling and design of effective drugs greatly depend upon the identification of suitable therapeutic targets. Several genetic determinants relating to proliferation and growth, invasion and metastasis have been identified. S100A4 appears to be able to activate and integrate pathways to generate the phenotypic responses that are characteristic of cancer. S100A4 signalling can focus on factors associated with normal and aberrant proliferation, apoptosis and growth, and differentiation. It is able to activate signalling pathways leading to the remodelling of the cell membrane and the extracellular matrix; modulation of cytoskeletal dynamics, acquisition of invasiveness and induction of angiogenesis. Therefore S100A4 is arguably a molecular target of considerable potential possessing a wide ranging biological activity that can alter and regulate the major phenotypic features of cancer. The evolution of an appropriate strategy that permits the identification of therapeutic targets most likely to be effective in the disease process without unduly affecting normal biological processes and function is an incontrovertible imperative. By virtue of its ability to activate interacting and multi-functional signalling systems, S100A4 appears to offer suitable targets for developing new therapeutic procedures. Some effectors of the S100A4-activated pathways might also lend themselves as foci of therapeutic interest.
authors.affiliation: School of Electrical, Electronic and Computer Engineering, University of Newcastle, Newcastle upon Tyne NE1 7RU, UK. gajanan.sherbet@ncl.ac.uk
authors.forename: G V
authors.initials: GV
authors.lastname: Sherbet
mesh_terms: D017209:Apoptosis; D002454:Cell Differentiation; D049109:Cell Proliferation; D003599:Cytoskeleton / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008954:Models, Biological; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism*; D009389:Neovascularization, Pathologic; D000071999:S100 Calcium-Binding Protein A4; D009418:S100 Proteins / Q000037:antagonists & inhibitors / Q000502:physiology*; D015398:Signal Transduction; D019714:Tissue Inhibitor of Metalloproteinases / Q000378:metabolism; D051153:Wnt Proteins / Q000378:metabolism
chemical_list: D000071999:S100 Calcium-Binding Protein A4; D009418:S100 Proteins; D019714:Tissue Inhibitor of Metalloproteinases; D051153:Wnt Proteins; C077591:S100A4 protein, human