A stemness-related ZEB1-MSRB3 axis governs cellular pliancy and cancer genome stability.

ABSTRACT: Genomic instability is a prominent driver of tumorigenesis. However, a significant fraction of human cancers display few genomic aberrations, suggesting alternative roads towards malignancy. Here, we show that the differentiation status of normal human mammary epithelial cells influences the early response to an oncogenic activation and determines the genetic routes towards tumorigenesis. Following an oncogenic insult, luminal progenitors and differentiated luminal cells undergo oxidative and DNA replication stress, initiating genomic instability. In contrast, mammary stem cells exhibit the innate capacity to withstand aberrant mitogenic activation, fostering malignant transformation. This property relies upon a pre-emptive program driven by the ZEB1 transcription factor and the methionine

ORGANISM(S): Homo sapiens

SUBMITTER: Arnaud Vigneron 

PROVIDER: E-MTAB-4145 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress