Journal
ONCOGENE
Volume 27, Issue 38, Pages 5115-5123Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/onc.2008.225
Keywords
cancer stem cells; p53; p63; Rho signaling; epigenetics; keratinocytes
Funding
- NIH [AR39190, AR054856]
- Swiss National Foundation
- European Union [LSHB-CT-2005-019067]
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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.
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