UBE2J2 promotes hepatocellular carcinoma cell epithelial-mesenchymal transition and invasionin vitro

Abstract

Ubiquitin-conjugating enzyme E2 J2 (UBE2J2) is an ubiquitin proteasome component that responds to proteotoxic stress. We found that UBE2J2 was highly expressed in cellular protrusions of HCCLM3 metastatic hepatocellular carcinoma (HC) cells. Immunohistochemical analyses showed that UBE2J2 was expressed at higher levels in HC patient tissues than in corresponding non-tumor tissues. Because cellular protrusions are important for cell invasion, we hypothesized that UBE2J2 promotes HC cell invasion. We used chip-based surface plasmon resonance (SPR) to assess possible mechanisms of UBE2J2-regulated HCCLM3 cell invasion. We found that p-EGFR interacted with UBE2J2, and this finding was confirmed by co-immunoprecipitation analysis. UBE2J2 overexpression activated endothelial-mesenchymal transition in the non-invasive SMMC7721 HC cell line, and promoted invasion. UBE2J2 silencing reduced HCCLM3 cell invasion and endocytosis, and downregulated p-EGFR expression. p-EGFR inhibition by lapatinib reduced UBE2J2-promoted cell invasion, suggesting p-EGFR is important for UBE2J2-mediated HCCLM3 cell invasion. These findings demonstrate that endocytosis by HC cells is closely related to invasion, and may provide new anti-HC therapeutic targets. UBE2J2 may also be a novel biomarker for clinical HC diagnosis.

Ubiquitin Proteasome Gene Signatures in Ependymoma Molecular Subtypes

“…We could not find information in the literature regarding UBE2J2 expression in EPN. However, Chen et al [ 119 ] reported higher expression of UBE2J2 protein in hepatocellular carcinoma compared to normal liver tissue, which was associated with increased epithelial to mesenchymal transition (EMT) in vitro, whereas UBE2J2 gene knockdown promoted EGFR expression [ 119 ]. UBE4B regulates the degradation of the tumor suppressor p53 in breast cancer [ 120 ] and UBE2Q1 has been proposed as a marker for high-grade serous ovarian cancer [ 121 ].…”

Genetic disruption of mammalian endoplasmic reticulum‐associated protein degradation: Human phenotypes and animal and cellular disease models

“…E2 family members are associated with various diseases including cancers, muscular atrophy, Parkinson's disease, Fanconi anemia and development disorders 114–116 . Among the ERAD related E2 enzymes, UBE2J2 expression profiles are associated with hepatocellular carcinoma 117 . Although neither UBE2J1 nor UBE2G2 is linked to any disease yet, the depletion of UBE2J1 in a mouse model displayed impaired spermatid development profile 91 .…”

“…[114][115][116] Among the ERAD related E2 enzymes, UBE2J2 expression profiles are associated with hepatocellular carcinoma. 117 Although neither UBE2J1 nor UBE2G2 is linked to any disease yet, the depletion of UBE2J1 in a mouse model displayed impaired spermatid development profile. 91 Although these members are well involved in the ERAD machinery, the knockout HEK293 and HeLa cell models were designed to comprehend their physiological functions rather than their participation in ERAD.…”

E2 ubiquitin-conjugating enzymes in cancer: Implications for immunotherapeutic interventions

“…UBE2J2 is involved in cancer cell invasion. Accordingly, overexpression of UBE2J2 has been detected in cell protrusions of HCCLM3 hepatocellular carcinoma cells [80]. However, further studies are required to understand the specific role(s) of UBE2J2 in promoting cancer progression.…”