Memory of stochastic single-cell apoptotic signaling promotes chemoresistance in neuroblastoma.

ABSTRACT: Gene expression noise is known to promote stochastic drug resistance through the elevated expression of individual genes in rare cancer cells. However, we now demonstrate that chemoresistant neuroblastoma cells emerge at a much higher frequency when the influence of noise is integrated across multiple components of an apoptotic signaling network. Using a JNK activity biosensor with longitudinal high-content and in vivo intravital imaging, we identify a population of stochastic, JNK-impaired, chemoresistant cells that exist because of noise within this signaling network. Furthermore, we reveal that the memory of this initially random state is retained following chemotherapy treatment across a series of in vitro, in vivo, and patient models. Using matched PDX models established at diagnosis

SUBMITTER: Hastings JF 

PROVIDER: S-EPMC9984174 | biostudies-literature | 2023 Mar

REPOSITORIES: biostudies-literature