Patient-Derived Mutant Forms of NFE2L2/NRF2 Drive Aggressive Murine Hepatoblastomas.

ABSTRACT:

Background & aims

Hepatoblastoma (HB), the most common pediatric liver cancer, often bears β-catenin mutations and deregulates the Hippo tumor suppressor pathway. Murine HBs can be generated by co-expressing β-catenin mutants and the constitutively active Hippo effector YAP^S127A. Some HBs and other cancers also express mutants of NFE2L2/NRF2 (NFE2L2), a transcription factor that tempers oxidative and electrophilic stress. In doing so, NFE2L2 either suppresses or facilitates tumorigenesis.

Methods

We evaluated NFE2L2's role in HB pathogenesis by co-expressing all combinations of mutant β-catenin, YAP^S127A, and the patient-derived NFE2L2 mutants L30P and R34P in murine livers. We evaluated growth, biochemical and metabolic profiles, and transcriptomes of

SUBMITTER: Wang H 

PROVIDER: S-EPMC8102178 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature