Nrf2 induces malignant transformation of hepatic progenitor cells by inducing β-catenin expression.

ABSTRACT: The Nrf2 signaling pathway prevents cancer initiation, but genetic mutations that activate this pathway are found in various types of cancer. The molecular mechanisms underlying this Janus-headed character are still not understood. Here, we show that sustained Nrf2 activation induces proliferation and dedifferentiation of a Wnt-responsive perivenular hepatic progenitor cell population, transforming them into metastatic cancer cells. The neoplastic lesions display many histological features known from human hepatoblastoma. We describe an Nrf2-induced upregulation of β-catenin expression and its activation as the underlying mechanism for the observed malignant transformation. Thus, we have identified the Nrf2-β-catenin axis promoting proliferation of hepatic stem cells and triggering tumorig

SUBMITTER: Fragoulis A 

PROVIDER: S-EPMC9618468 | biostudies-literature | 2022 Nov

REPOSITORIES: biostudies-literature