title: Mechanisms of oncogenic cooperation in cancer initiation and metastasis.
abstract: Cancer is a disease of extreme heterogeneity. Microarray analysis has identified thousands of genes that are transcriptionally up- or down-regulated in tumor samples; molecularly characterized lesions that play a causative role in tumorigenesis constitute more than 1 percent of the human genome. Such a large number of "cancer genes" stirs the debate of whether it is relevant to continue classifying cancer as a single condition. Yet, a discrete set of cellular processes has been found to underlie such complexity. Their deregulation has been proposed to act as a common denominator that enables tumors to evade cellular barriers to proliferation and metastasis. Efforts have been made to identify and model the mechanistic origins of cancer. Two such models are discussed here: the multistage model of cancer and the cancer platform model. The former suggests cancer arises by the sequential acquisition of mutations leading to the progressive erosion of normal cellular control mechanisms. In contrast, the latter reduces cancer initiation to two interdependent conditions: sustained proliferation with the concomitant inhibition of cell death. This review proposes that a third condition - cellular differentiation - should be added to the cancer platform model. Differentiation can act as a fail-safe mechanism against unrestrained cellular growth - much like cell death. Clinical implications of the different models are also analyzed.
authors.affiliation: Department of Genetics, Yale University School of Medicine, New Haven, Connecticut 06536, USA. lpedraza@law.harvard.edu
authors.forename: Laura G
authors.initials: LG
authors.lastname: Pedraza-Fariña
mesh_terms: D000818:Animals; D017209:Apoptosis; D002453:Cell Cycle; D002454:Cell Differentiation; D019070:Cell Lineage; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic; D016922:Cellular Senescence; D018450:Disease Progression; D015972:Gene Expression Regulation, Neoplastic; D016678:Genome; D006801:Humans; D009154:Mutation; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D009369:Neoplasms / Q000378:metabolism* / Q000473:pathology*; D009857:Oncogenes / Q000235:genetics*; D015398:Signal Transduction