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Stress-induced epinephrine promotes hepatocellular carcinoma progression via the USP10-PLAGL2 signaling loop.
- Source :
-
Experimental & molecular medicine [Exp Mol Med] 2024 May; Vol. 56 (5), pp. 1150-1163. Date of Electronic Publication: 2024 May 01. - Publication Year :
- 2024
-
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.<br /> (© 2024. The Author(s).)
- Subjects :
- Humans
Animals
Mice
Cell Line, Tumor
Disease Progression
Male
Stress, Physiological
Cell Proliferation
Carcinoma, Hepatocellular metabolism
Carcinoma, Hepatocellular pathology
Carcinoma, Hepatocellular etiology
Carcinoma, Hepatocellular genetics
Liver Neoplasms metabolism
Liver Neoplasms pathology
Liver Neoplasms etiology
Liver Neoplasms genetics
Epinephrine metabolism
Epinephrine pharmacology
Signal Transduction drug effects
RNA-Binding Proteins metabolism
RNA-Binding Proteins genetics
Ubiquitin Thiolesterase metabolism
Ubiquitin Thiolesterase genetics
DNA-Binding Proteins metabolism
DNA-Binding Proteins genetics
Transcription Factors metabolism
Transcription Factors genetics
Gene Expression Regulation, Neoplastic drug effects
Subjects
Details
- Language :
- English
- ISSN :
- 2092-6413
- Volume :
- 56
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- Experimental & molecular medicine
- Publication Type :
- Academic Journal
- Accession number :
- 38689092
- Full Text :
- https://doi.org/10.1038/s12276-024-01223-0