Escape from oncogene-induced senescence is controlled by POU2F2 and memorized by chromatin scars.

ABSTRACT: Although oncogene-induced senescence (OIS) is a potent tumor-suppressor mechanism, recent studies revealed that cells could escape from OIS with features of transformed cells. However, the mechanisms that promote OIS escape remain unclear, and evidence of post-senescent cells in human cancers is missing. Here, we unravel the regulatory mechanisms underlying OIS escape using dynamic multidimensional profiling. We demonstrate a critical role for AP1 and POU2F2 transcription factors in escape from OIS and identify senescence-associated chromatin scars (SACSs) as an epigenetic memory of OIS detectable during colorectal cancer progression. POU2F2 levels are already elevated in precancerous lesions and as cells escape from OIS, and its expression and binding activity to cis-regulatory ele

SUBMITTER: Martinez-Zamudio RI 

PROVIDER: S-EPMC10112333 | biostudies-literature | 2023 Apr

REPOSITORIES: biostudies-literature