Speaker: Dr. Pier Giuseppe Pelicci
European Institute of Oncology, Milan
FIRC Institute of Molecular Oncology (IFOM), Milan

Host

Cayetano González, IRB Barcelona

Friday, 22 January 2010, 12.00h Aula Fèlix Serratosa

Abstract

Recent findings support the concept that cells with the properties of stem cells (SC) are integral to the development and perpetuation of several forms of human cancer, and that eradication of cancer stem cells (CSC) may be essential to achieve cancer cure. However, direct proof of these concepts is still lacking, mainly due the scarcity of appropriate model systems. We are characterizing the biological differences between normal and transformed SCs. SCs are defined by their abilities to generate more SCs (‘self-renewal’) and to produce cells that differentiate. One mechanism by which SCs accomplish these two tasks is asymmetric cell division, whereby each SC divides to generate one daughter with SC fate and one that differentiates. SCs, however, possess the ability to expand in number, as it occurs during development and in adulthood after injury or disease. This increase is not accounted by asymmetric divisions, in which only one daughter cell maintains SC identity. Recent findings in C.elegans and Drosophila indicate that SCs can also generate daughter cells that are destined to acquire the same fate (symmetric cell division). On the other hand, SC quiescence is critical to maintain tissue homeostasis after injury. We will present our recent findings showing increased symmetric divisions of CSCs in breast tumors (due to inactivation of the p53 tumor suppressor) and dependency of leukemia development on quiescent leukemia SCs (due to transcriptional up-regulation of the cell cycle inhibitor p21 by leukemiaassociated fusion proteins). Our findings suggest that that asymmetric divisions of stem cells function as a mechanism of tumor suppression, that SC quiescence is critical to the maintenance of the transformed clone and that symmetric divisions of SCs permits its geometric expansion.

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