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Inside mechanisms sustaining cancer stem cells

Final Report Summary - INMEC (Inside mechanisms sustaining cancer stem cells)

The most recent hypothesis on cancer progression implies the existence of a rare subset of cancer cells, the so called Cancer Stem Cells, endowed with “self-renewal” properties and thus responsible for tumor growth and maintenance. This hypothesis implies that Cancer Stem Cells must be eliminated to completely eradicate the tumor. However, direct proof of such hypothesis is still lacking.
We have previously demonstrated that the self-renewal ability of Cancer Stem Cells -a feature required for the maintenance of a Cancer Stem Cell pool and for tumor growth- is linked to the tumor suppressor p53 and the cell cycle inhibitor p21. Specifically, i) an increased frequency of symmetric divisions due to inactivation of p53; ii) increased replicative potential due to upregulation of p21.
The objective of this proposal was to explore the intrinsic, cellular mechanisms responsible for the altered self-renewal of cancer stem cells affecting tumor growth and tumor heterogeneity.
Our results determined how cancer stem cells contribute to the generation of tumor heterogeneity and to tumor growth, and strongly suggest mechanisms for leukemia maintenance and relapse.