MyD88 in myofibroblasts regulates aerobic glycolysis‐driven hepatocarcinogenesis via ERK‐dependent PKM2 nuclear relocalization and activation

• DOI: 10.1002/path.5856
• Publication Date: 2021-12-20T05:15:04Z
• Authors: Qi Yuan; Jie Zhang; Yu Liu; Haiqiang Chen; Haiyang Liu; Jinyan Wang; Meng Niu; Lingling Hou; Zhenlong Wu; Zhinan Chen; Jinhua Zhang
• Keywords: PKM2; Anaerobic glycolysis

Abstract Hepatic stellate cells (HSCs) and cancer‐associated fibroblasts (CAFs) play critical roles in liver fibrosis hepatocellular carcinoma (HCC). MyD88 controls the expression of several key modifier genes tumorigenesis; however, whether how myofibroblasts contributes to development fibrosis‐associated cancer remains elusive. Here, we used an established hepatocarcinogenesis mouse model involving apparent fibrogenesis which was selectively depleted myofibroblasts. Myofibroblast MyD88‐deficient (Fib‐MyD88 KO) mice developed significantly fewer smaller tumor nodules. deficiency attenuated aerobic glycolysis tissues. Mechanistically, signaling increased secretion CCL20, promoted cells. This process dependent on CCR6 receptor ERK/PKM2 signaling. Furthermore, growth greatly relieved when were treated with a inhibitor. Our data revealed role for promotion by affecting might provide potential molecular therapeutic target HCC. © 2021 The Pathological Society Great Britain Ireland.