Abstract

Different theories have been proposed to explain tumour heterogeneity including the cancer cell of origin. Here, we developed genetically engineered mouse models allowing lineage tracing together with oncogenic activation in different cell lineages of the skin epidermis and the mammary gland and assessed whether the cancer cell of origin controls tumour heterogeneity. I will discuss evidence that the cancer cell of origin controls tumour heterogeneity and the underlying molecular mechanisms that promote tumor differentiation, propagation, EMT and metastasis in primary tumors. These results have important implications for our understanding of the mechanisms controlling tumor heterogeneity and the development of new strategies to block tumor initiation. This work is supported by the ERC , WELBIO, the FNRS , the Fondation Bettencourt-Schuler and the Fondation Baillet-Latour