Sustained activation of detoxification pathways promotes liver carcinogenesis in response to chronic bile acid-mediated damage.

ABSTRACT: Chronic inflammation promotes oncogenic transformation and tumor progression. Many inflammatory agents also generate a toxic microenvironment, implying that adaptive mechanisms must be deployed for cells to survive and undergo transformation in such unfavorable contexts. A paradigmatic case is represented by cancers occurring in pediatric patients with genetic defects of hepatocyte phosphatidylcholine transporters and in the corresponding mouse model (Mdr2-/- mice), in which impaired bile salt emulsification leads to chronic hepatocyte damage and inflammation, eventually resulting in oncogenic transformation. By combining genomics and metabolomics, we found that the transition from inflammation to cancer in Mdr2-/- mice was linked to the sustained transcriptional activation of metabolic de

SUBMITTER: Collino A 

PROVIDER: S-EPMC5957449 | biostudies-literature | 2018 May

REPOSITORIES: biostudies-literature