Nrf2 Mutation/Activation Is Dispensable for the Development of Chemically Induced Mouse HCC

Abstract

Unlike human and rat hepatocellular carcinoma, chemically induced mouse hepatocellular carcinomas do not show Nrf2 mutation/activation. Furthermore, metabolic reprogramming of neoplastic cells is absent as well. The results suggest that the mouse is not the ideal model to investigate the role of nuclear factor (erythroid-derived 2)-like 2 in hepatocarcinogenesis.

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

“…Mechanistic studies in animal models of liver carcinogenesis described a synergistic effect of Nrf2 and β-catenin in cancer initiation and progression. Most Recently, Mattu et al showed that a gain of function mutation of the gene for Nrf2 is not mandatory for the development of chemically induced HCC in mice but not in human and rat [ 61 ]. Nevertheless, Zavattari et al (2015) showed that Nrf2 is activated early in HCC formation and is probably essential for clonal expansion of preneoplastic hepatocytes.…”

The multifaceted perspectives on the regulation of lncRNAs in hepatocellular carcinoma ferroptosis: from bench-to-bedside

“…However, in the presence of cellular stress, Keap1 undergoes conformational changes, blocking NRF2 degradation and allowing its nuclear translocation, leading to the transactivation of antioxidant genes, thus inhibiting ferroptosis [ 61 , 62 ]. In HCC, NRF2 mutations accounted for approximately 15% of patients [ 63 ]. When HCC cells were exposed to ferroptosis inducers including sorafenib, buthionine sulfoximine, and erastin, there was an upregulation of p62 [ 64 , 65 ].…”