Fig. 1

The mechanism by which hepatocytes express and secrete FGL1 under physiological and pathological conditions. a FGL1 has two origins, with the liver being the classic source. FGL1 secreted by the liver can be distributed in adipose tissue and circulate in the blood. Tumor tissues, such as cancerous lung tissues (e.g., NSCLC), were recently identified as a new source of FGL1; FGL1 can also be detected on the surface of CTCs in NSCLC patients. FGL1 acts on both adipocytes and myoblasts via exerting telecrine effects. b The mechanism of normal hepatocyte expression and secretion of FGL1 under physiological conditions: In normal hepatocytes, the JAK2-STAT3 pathway is activated by either the inflammatory factor IL-6 or radiation. HNF1α forms a complex by binding to the HMGB1 and CREB proteins in the cytoplasm. Then, it enters the nucleus and binds to the HPS promoter through pSTAT3, thereby upregulating FGL1 transcription. The overexpressed FGL1 protein is distributed via an autocrine process. c The mechanism of low FGL1 expression in HCC: The IL-6-JAK2-STAT3 pathway, which induces FGL1 expression, can be blocked by oxysophocarpine (OSP). Deletion of HNF1α and inhibition of the AKT-mTOR pathway downregulate FGL1 via an endocrine mechanism