dataset
posted on 2023-03-31, 02:02 authored by Gabriela Koifman, Yoav Shetzer, Shay Eizenberger, Hilla Solomon, Ron Rotkopf, Alina Molchadsky, Giuseppe Lonetto, Naomi Goldfinger, Varda Rotter IPA analysis of the differential genes between p53 Mut MSC TL and KO MSC TL sub-clones. Biological functions and pathway analysis were determined for the upregulated and downregulated genes following p53 Mut KO. (The threshold of significant genes; padj<0.05, -2>FC>2, max reads>10)
Funding
Israel Science Foundation
Flight Attendant Medical Research Institute
Israel Cancer Research Fund (ICRF)
History
ARTICLE 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 expressed in human tumors harboring p53 hotspot mutations. These data indicate that the ESC gene signature–derived genes may serve as new stemness-based prognostic biomarkers as well as novel cancer therapeutic targets.Significance: Mesenchymal cancer stem cell-like cell lines express a mutant p53-dependent embryonic stem cell gene signature, which can serve as a potential prognostic biomarker and therapeutic target in cancer. Cancer Res; 78(20); 5833–47. ©2018 AACR.
