Stress-induced epinephrine promotes hepatocellular carcinoma progression via the USP10-PLAGL2 signaling loop

Hepatocellular carcinoma (HCC) is associated with a poor prognosis. Our previous study demonstrated that Pleomorphic adenoma gene like-2 (PLAGL2) was a potential therapeutic target in HCC. However, the mechanisms that lead to the upregulation of PLAGL2 in HCC remain unclear. The present study revealed that stress-induced epinephrine increased the expression of PLAGL2, thereby promoting the progression of HCC. Furthermore, PLAGL2 knockdown inhibited epinephrine-induced HCC development. Mechanistically, epinephrine upregulated ubiquitin-specific protease 10 (USP10) to stabilize PLAGL2 via the adrenergic beta-receptor-2-c-Myc (ADRB2-c-Myc) axis. Furthermore, PLAGL2 acted as a transcriptional regulator of USP10, forming a signaling loop. Taken together, these results reveal that stress-induced epinephrine activates the PLAGL2-USP10 signaling loop to enhance HCC progression. Furthermore, PLAGL2 plays a crucial role in psychological stress-mediated promotion of HCC progression. Hepatocellular carcinoma (HCC, a type of liver cancer) is a major cause of cancer deaths globally, with high chances of recurrence and spread. Scientists discovered that the protein PLAGL2 contributes to HCC's growth and spread, but it's unclear how its levels increase. Weiwei Hu and his team aimed to explore this. They performed various tests using HCC tissues, cell cultures, and mice. They discovered that long-term stress, specifically the hormone epinephrine, boosts the production of PLAGL2 and HCC progression. This study offers new understanding of stress's role in cancer progression and potential targets for HCC treatment. The scientists concluded that more research is required to fully comprehend these results for future cancer therapies.This summary was initially drafted using artificial intelligence, then revised and fact-checked by the author.