Abstract
Cancer development results from deregulated control of stem cell populations and alterations in their surrounding environment. Notch signaling is an important form of direct cell-cell communication involved in cell fate determination, stem cell potential and lineage commitment. The biological function of this pathway is critically context dependent. Here we review the pro-differentiation role and tumor suppressing function of this pathway, as revealed by loss-of-function in keratinocytes and skin, downstream of p53 and in cross-connection with other determinants of stem cell potential and/or tumor formation, such as p63 and Rho/CDC42 effectors. The possibility that Notch signaling elicits a duality of signals, involved in growth/differentiation control and cell survival will be discussed, in the context of novel approaches for cancer therapy.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
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Review
MeSH terms
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Animals
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Apoptosis / physiology
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Cell Differentiation / physiology
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Cell Transformation, Neoplastic / genetics
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DNA Damage
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Female
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Genes, Tumor Suppressor
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Humans
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Keratinocytes / pathology
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Keratinocytes / radiation effects
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Mice
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Neoplasms / genetics*
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Neoplasms / physiopathology
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Neoplasms / virology
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Oncogene Proteins, Viral / physiology
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Receptor, Notch1 / genetics
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Receptor, Notch1 / physiology
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Receptors, Notch / genetics
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Receptors, Notch / physiology*
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Signal Transduction / physiology
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Species Specificity
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Tumor Suppressor Protein p53 / physiology
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Tumor Suppressor Proteins / genetics
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Tumor Suppressor Proteins / physiology*
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Tumor Virus Infections / physiopathology
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Ultraviolet Rays / adverse effects
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Uterine Cervical Neoplasms / genetics
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Uterine Cervical Neoplasms / physiopathology
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Uterine Cervical Neoplasms / virology
Substances
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NOTCH1 protein, human
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Notch1 protein, mouse
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Oncogene Proteins, Viral
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Receptor, Notch1
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Receptors, Notch
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Tumor Suppressor Protein p53
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Tumor Suppressor Proteins