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

Exp Mol Med. 2024 May 1. doi: 10.1038/s12276-024-01223-0. Online ahead of print.ABSTRACTHepatocellular 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 β-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.PMID:38689092 | DOI:10.1038/s12276-024-01223-0

Source: Molecular Medicine - April 30, 2024 Category: Molecular Biology Authors: Chen Wang Jiaping Ni Dongqing Zhai Yanchao Xu Zijie Wu Yuyuan Chen Ning Liu Juan Du Yumeng Shen Guilai Liu Yong Yang Linjun You Weiwei Hu Source Type: research