No abstract

During lung inflammation, IL-33 and leukotrienes synergistically induce ILC2s. ILC2s are a highly pathogenic and unexpected source for IL-17 in lung inflammation.

α-Enolase 1 (ENO1) is a critical glycolytic enzyme whose aberrant expression drives the pathogenesis of various cancers. ENO1 has been indicated to have additional roles beyond its conventional metabolic activity, but the underlying mechanisms and biological consequences remain elusive. Here, we show that ENO1 suppresses iron regulatory protein 1 (IRP1) expression to regulate iron homeostasis and survival of hepatocellular carcinoma (HCC) cells. Mechanistically, we unprecedentedly uncover that ENO1, as an RNA-binding protein, recruits CNOT6 to accelerate the mRNA decay of IRP1 in cancer cells, leading to inhibition of mtioferin-1 (Mfrn1) expression and subsequent repression of mitochondrial iron-induced ferroptosis. Moreover, through in vitro and in vivo experiments and clinical sample analysis, we identified IRP1 and Mfrn1 as tumor suppressors by inducing ferroptosis in HCC cells.