Emmanuelle Passegué, PhD

Core

Not every cancer cell is capable of producing a tumor. In fact, the vast majority of them are unable to sustain tumor growth despite being responsible for most of the clinical symptoms. Increasing numbers of cancers are now been shown to arise from a rare subset of cancer cells, the so-called “cancer-initiating stem cells” or “cancer stem cells” (CSC), which escape normal regulation and drive the formation and growth of the tumors. While the role of stem cells in normal development, physiology, tissue homeostasis and regeneration upon stress or injury has been long recognized, the fact that cancer has its roots in either the direct oncogenic transformation of stem cells or in cells that have re-acquire stem cell characteristics is an emerging concept is cancer biology. As a consequence, there is still a plethora of features about CSC that remain to be addressed. However, the potential importance of CSC to our understanding of cancer initiation, progression and therapy certainly cannot be understated.

Our work investigates how regulation of fundamental processes that are involved in the maintenance of normal stem cell functions, such as proliferation, apoptosis, genome stability, and interaction with the microenvironment, are affected in CSC. Our goal is to understand how deregulations of these molecular and cellular mechanisms contribute to CSC generation and function, and how CSC are involved in cancer evolution. To address these questions, we are using a mouse model of blood cancer —leukemia—in which the blood-forming hematopoietic stem cells (HSC) have been identified as the CSC population. Our work is aimed at providing new molecular insights into the signaling pathways that distinguish CSC from normal stem cells to help with the design of novel anti-cancer therapies that will specifically target CSC and their aberrant properties.