Gabriela Koifman
Weizmann Institute of Science, Israel
Title: Mutant p53 leads to enrichment of cancer stem cells that display ESC expression signature
Biography
Biography: Gabriela Koifman
Abstract
Mutation in the p53 gene is a frequent alteration in human cancers which mostly leads to the acquiring of new oncogenic functions that promote tumorigenesis. In this study, we observed that bone marrow derived from mutant p53 mice exhibit higher ability to form tumors compared to WT-MSCs. Cultivation of tumors obtained from mutant p53 MSCs led to the selection of aggressive tumor-derived cell lines with an enhanced tumorigenic capacity as compared with their parental MSCs. The newly established tumor-derived cell lines were able to generate tumors following injection of as few as 100 cells, as well as displayed high expression of embryonic stem cell (ESC) signature. We were able to show that the enhanced tumor initiating capacity and the expression of ESC signature exhibited by the tumor-derived cell lines is mutant p53 dependent. In order to confirm our findings in human settings, we utilized datasets from The Cancer Genome Atlas (TCGA). Expression levels of genes belonging to the ESC signature expressed by mutant p53 derived tumor cell lines were examined in human tumors harboring p53 missense mutation. In agreement with data obtained from mouse models, we identified 41 genes that were significantly and exclusively upregulated in human tumors harboring p53 missense mutation. In conclusion, our results suggest that mutant p53 oncogenic GOF in MSCs leads to the acquirement of CSC features, including enhanced expression of ESC signature. This ESC signature might assist to design a more specific cancer stem-cells targeted therapy for Li-Fraumeni patients and cancer at large.