Id proteins at the cross-road of development and cancer.
A large body of evidence has been accumulated that demonstrates dominant effects of Id proteins on different aspects of cellular growth. Generally, constitutive expression of Id not only blocks cell differentiation but also drives proliferation. In some settings, it is sufficient to render cells immortal or induce oncogenic transformation. The participation of Id proteins in advanced human malignancy, where they are frequently deregulated, has been dramatically bolstered by the recent discovery that Id exert pivotal contributions to many of the essential alterations that collectively dictate malignant growth. Relentless proliferation associated with self-sufficiency in growth signals and insensitivity to growth inhibitory signals, sustained neoangiogenesis, tissue invasiveness and migration capabilities of tumor cells all share dependency on the unlimited availability of Id proteins. It is remarkable that many of these features recapitulate those physiologically propelled by Id proteins to support normal development. We propose that the participation of Id in multiple fundamental traits of cancer may be the basis for unprecedented therapeutic opportunities.
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Department of Neurology, Developmental and Molecular Biology, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
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Iavarone
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D000818:Animals; D018797:Cell Cycle Proteins / Q000502:physiology; D002455:Cell Division / Q000235:genetics / Q000502:physiology; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000502:physiology*; D005544:Forecasting; D018507:Gene Expression Regulation, Developmental; D015972:Gene Expression Regulation, Neoplastic; D016161:Genes, Retinoblastoma; D006801:Humans; D051798:Inhibitor of Differentiation Protein 1; D051797:Inhibitor of Differentiation Protein 2; D051796:Inhibitor of Differentiation Proteins; D005810:Multigene Family; D009361:Neoplasm Invasiveness / Q000235:genetics; D009363:Neoplasm Proteins / Q000235:genetics / Q000502:physiology; D009369:Neoplasms / Q000235:genetics; D009374:Neoplasms, Experimental / Q000235:genetics; D009380:Neoplasms, Nerve Tissue / Q000235:genetics; D009389:Neovascularization, Pathologic / Q000235:genetics; D009857:Oncogenes; D012097:Repressor Proteins; D016160:Retinoblastoma Protein / Q000502:physiology; D015398:Signal Transduction; D014157:Transcription Factors / Q000235:genetics / Q000502:physiology*
D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; C497453:ID1 protein, human; C497450:ID2 protein, human; C490128:ID4 protein, human; D051798:Inhibitor of Differentiation Protein 1; D051797:Inhibitor of Differentiation Protein 2; D051796:Inhibitor of Differentiation Proteins; D009363:Neoplasm Proteins; D012097:Repressor Proteins; D016160:Retinoblastoma Protein; D014157:Transcription Factors; C075640:ID3 protein, human