A Mutant p53-Dependent Embryonic Stem Cell Gene Signature Is Associated with Augmented Tumorigenesis of Stem Cells

Cancer Research
Gabriela KoifmanVarda Rotter

Abstract

Mutations in the tumor suppressor p53 are the most frequent alterations in human cancer. These mutations include p53-inactivating mutations as well as oncogenic gain-of-function (GOF) mutations that endow p53 with capabilities to promote tumor progression. A primary challenge in cancer therapy is targeting stemness features and cancer stem cells (CSC) that account for tumor initiation, metastasis, and cancer relapse. Here we show that in vitro cultivation of tumors derived from mutant p53 murine bone marrow mesenchymal stem cells (MSC) gives rise to aggressive tumor lines (TL). These MSC-TLs exhibited CSC features as displayed by their augmented oncogenicity and high expression of CSC markers. Comparative analyses between MSC-TL with their parental mutant p53 MSC allowed for identification of the molecular events underlying their tumorigenic properties, including an embryonic stem cell (ESC) gene signature specifically expressed in MSC-TLs. Knockout of mutant p53 led to a reduction in tumor development and tumorigenic cell frequency, which was accompanied by reduced expression of CSC markers and the ESC MSC-TL signature. In human cancer, MSC-TL ESC signature-derived genes correlated with poor patient survival and were highly ex...Continue Reading

Citations

Dec 28, 2019·Journal of Molecular Cell Biology·Gabriela KoifmanVarda Rotter
Nov 30, 2019·European Heart Journal·Marcin Wysoczynski, Roberto Bolli
Dec 11, 2019·International Journal of Molecular Sciences·Yan SteinRonit Aloni-Grinstein
Dec 15, 2019·International Journal of Molecular Sciences·Consuelo PitolliIvano Amelio
Nov 24, 2020·Stem Cell Reviews and Reports·Alaleh RezalotfiNima Rezaei
Nov 20, 2020·Scientific Reports·Alexander PlotnikovHaim Michael Barr
Feb 23, 2021·Frontiers in Oncology·Yong ShiHelin Vakifahmetoglu-Norberg

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