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lüll Notch tumor suppressor function Dotto GPOncogene 2008[Sep]; 27 (38): 5115-23Cancer 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.|Animals[MESH]|Apoptosis/physiology[MESH]|Cell Differentiation/physiology[MESH]|Cell Transformation, Neoplastic/genetics[MESH]|DNA Damage[MESH]|Female[MESH]|Genes, Tumor Suppressor[MESH]|Humans[MESH]|Keratinocytes/pathology/radiation effects[MESH]|Mice[MESH]|Neoplasms/*genetics/physiopathology/virology[MESH]|Oncogene Proteins, Viral/physiology[MESH]|Receptor, Notch1/genetics/physiology[MESH]|Receptors, Notch/genetics/*physiology[MESH]|Signal Transduction/physiology[MESH]|Species Specificity[MESH]|Tumor Suppressor Protein p53/physiology[MESH]|Tumor Suppressor Proteins/genetics/*physiology[MESH]|Tumor Virus Infections/physiopathology[MESH]|Ultraviolet Rays/adverse effects[MESH]|Uterine Cervical Neoplasms/genetics/physiopathology/virology[MESH] |