The role of apoptosis in tumor progression and metastasis.
Metastasis, the process by which cancer spreads from a primary to a secondary site, is responsible for the majority of cancer related deaths. Yet despite the detrimental effects of metastasis, it is an extremely inefficient process by which very few of the cells that leave the primary tumor give rise to secondary tumors. Metastasis can be considered as a series of sequential steps that begins with a cell leaving a primary tumor, and concludes with the formation of a metastatic tumor in a distant site. During the process of metastasis cells are subjected to various apoptotic stimuli. Thus, in addition to genetic changes that promote unregulated proliferation, successful metastatic cells must have a decreased sensitivity to apoptotic stimuli. As many cancer cells exhibit aberrations in the level and function of key apoptotic regulators, exploiting these alterations to induce tumor cell apoptosis offers a promising therapeutic target. This review will examine the apoptotic regulators that are often aberrantly expressed in metastatic cells; the role that these regulators may play in metastasis; the steps of metastasis and their susceptibility to apoptosis; and finally, current and future cancer prognostics and treatment targets based on apoptotic regulators.
Department of Medical Biophysics, University of Western Ontario, London, Canada N6A 4L6.
Jason L
JL
Townson
George N
GN
Naumov
Ann F
AF
Chambers
D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D015972:Gene Expression Regulation, Neoplastic; D019254:Genes, bcl-2; D006801:Humans; D009362:Neoplasm Metastasis; D009369:Neoplasms / Q000628:therapy; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism; D018631:ras Proteins / Q000235:genetics / Q000378:metabolism
D016159:Tumor Suppressor Protein p53; D018631:ras Proteins