Are you sure you want to leave this community? Leaving the community will revoke any permissions you have been granted in this community.
Obesity increases the incidence of hepatocellular carcinoma (HCC) development in part through the activation of obesity-associated proinflammatory signaling. Here, we show that in lean mice, abrogation of IL-6Rα signaling protects against diethylnitrosamine (DEN)-induced HCC development. HCC protection occurs via Mcl-1 destabilization, thus promoting hepatocyte apoptosis. IL-6 regulates Mcl-1 stability via the inhibition of PP-1α expression, promoting GSK-3β inactivation. In addition, IL-6 suppresses expression of the Mcl-1 E3 ligase (Mule). Consequently, IL-6Rα deficiency activates PP-1α and Mule expression, resulting in increased Mcl-1 turnover and protection against HCC development. In contrast, in obesity, inhibition of PP-1α and Mule expression, leading to Mcl-1 stabilization, occurs independently of IL-6 signaling. Collectively, this study provides evidence that obesity inhibits hepatocyte apoptosis through Mcl-1 stabilization independent of IL-6 signaling, thus promoting liver carcinogenesis.
Pubmed ID: 23954788
Publication data is provided by the National Library of Medicine ® and PubMed ®. Data is retrieved from PubMed ® on a weekly schedule. For terms and conditions see the National Library of Medicine Terms and Conditions.
Privately held company that develops and produces antibodies, ELISA kits, ChIP kits, proteomic kits, and other related reagents used to study cell signaling pathways that impact human health.
View all literature mentionsImaris provides range of capabilities for working with three dimensional images. Uses flexible editing and processing functions, such as interactive surface rendering and object slicing capabilities. And output to standard TIFF, Quicktime and AVI formats. Imaris accepts virtually all image formats that are used in confocal microscopy and many of those used in wide-field image acquisition.
View all literature mentions