The epidermal growth factor system of ligands and receptors in cancer

Autor: William J. Gullick
Rok vydání: 2009
Předmět:
Zdroj: European Journal of Cancer. 45:205-210
ISSN: 0959-8049
Popis: Multicellular organisms have evolved systems to allow information to be exchanged between cells in tissues. One example of these utilises proteins or peptides which are synthesised and released under stringent controls from one cell which then diffuse through the interstitial space until they encounter another cell which possesses cell surface proteins which bind this “first” messenger. These latter proteins, termed receptors, alter their activity and convey information across the plasma cell membrane to the cytoplasm, the “second” message, to elicit responses which include inducing the cell to exit a quiescent state and to enter the cell replicative cycle or to induce the cell to transit this cycle more rapidly. Other responses may also occur such as alterations in the cell cytoskeleton which may affect motility or the release of further signals such as those inducing neovascularisation. Typically in normal tissues these act during development or are evoked in processes such as wound healing. Mutations in genes involved directly or indirectly with these systems can activate this program of events [1], recapitulating the wound healing response. However, due to the fixation of the mutations this process cannot be switched off, hence the remark that “cancer is a wound that never heals”. It is no surprise therefore that aberrant activation of signalling pathways is inevitably associated with processes such as the secretion of proteolytic enzymes, which digest basement membranes, and the promotion of revascularisation, which are both essential to the spread and growth of solid tumours. In fact few mutations have been identified in genes which participate in these “secondary” events, presumably as they are necessary but insufficient in themselves to act as drivers of metastatic cancer [2]. One subset of growth factors and their receptors quite frequently involved in instigating and maintaining cell transformation are the receptor tyrosine kinases (RTKs). There are 58 RTK genes present in the human genome which can be subdivided into several families based on their sequence similarity, the similarity of their ligands and their known physical and functional interactions [3]. Some of these receptor types have barely been studied at all, but one family, partially because of its prominence in tumour development, is now known in some detail and has suggested paradigms which may (or may not) be instructive in the study of other less regarded receptors. This is the epidermal growth factor receptor (EGFR) family which consists of four receptors and (at least) eleven growth factors [4].
Databáze: OpenAIRE
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