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PSMC2 promotes hepatocellular carcinoma progression through interaction with EGFR
Yecheng Li1,2, Qunxue Su3, Zhenyu Feng2
1Suzhou Institute of Nano-Tech and Nano-Bionics, Chinese Academy of Sciences, Suzhou, 215123, China.
Clinical and Experimental Medicine
|May 24, 2026
Summary
Proteasome 26S Subunit ATPase 2 (PSMC2) is overexpressed in hepatocellular carcinoma (HCC), promoting cancer growth and metastasis. Targeting PSMC2 may offer a new therapeutic strategy for HCC patients.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- The ubiquitin-proteasome system is crucial in cancer development.
- Proteasome 26S Subunit ATPase 2 (PSMC2) is a key proteasome component implicated in various cancers.
- The specific role of PSMC2 in hepatocellular carcinoma (HCC) progression is not well understood.
Purpose of the Study:
- To investigate the expression and function of PSMC2 in HCC.
- To elucidate the underlying molecular mechanisms of PSMC2 in HCC progression.
- To evaluate PSMC2 as a potential prognostic biomarker and therapeutic target for HCC.
Main Methods:
- Analysis of PSMC2 expression in The Cancer Genome Atlas (TCGA) database, clinical HCC specimens, and cell lines using immunohistochemistry (IHC) and Western blot.
- In vitro functional assays (CCK-8, colony formation, scratch, transwell invasion) to assess HCC cell proliferation, migration, and invasion.
- In vivo xenograft models and mechanistic studies (co-immunoprecipitation, Western blot, immunofluorescence) to investigate PSMC2-EGFR interactions and downstream signaling pathways (AKT, ERK1/2).
Main Results:
- PSMC2 was significantly overexpressed in HCC tissues and correlated with poor patient prognosis.
- PSMC2 knockdown inhibited HCC cell proliferation, migration, and invasion in vitro and suppressed tumor growth in vivo.
- PSMC2 physically interacted with EGFR, stabilizing its protein levels and enhancing AKT and ERK1/2 phosphorylation, thereby activating downstream signaling.
Conclusions:
- PSMC2 acts as a novel oncogene in HCC progression by stabilizing EGFR and activating the EGFR-AKT/ERK1/2 signaling axis.
- PSMC2 is a potential prognostic biomarker for HCC.
- PSMC2 represents a promising therapeutic target for HCC intervention.
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