Nrf2 prevents Notch-induced insulin resistance and tumorigenesis in mice.

ABSTRACT: Insulin resistance is associated with increased incidence and enhanced progression of cancers. However, little is known about strategies that can effectively ameliorate insulin resistance and consequently halt cancer progression. Herein, we propose that the transcription factor Nrf2 (also known as Nfe2l2) may be such a target, given its central role in disease prevention. To this end, we developed a mouse that overexpresses the Notch intracellular domain in adipocytes (AdNICD), leading to lipodystrophy-induced severe insulin resistance and subsequent development of sarcomas, as a model reflecting that Notch signaling is deregulated in cancers and shows positive associations with insulin resistance and fatty liver disease in humans. Nrf2 pathway activation was achieved by knocking down Keap

SUBMITTER: Chartoumpekis DV 

PROVIDER: S-EPMC5922294 | biostudies-literature | 2018 Mar

REPOSITORIES: biostudies-literature