Stress-induced Epinephrine Promotes Hepatocellular Carcinoma Progression Via the USP10-PLAGL2 Signaling Loop

Overview

Journal Exp Mol Med

Specialties Biochemistry
Molecular Biology

Date 2024 Apr 30

PMID 38689092

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

Affiliations

Soon will be listed here.

Abstract

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 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.

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