UBE2J2 promotes hepatocellular carcinoma cell epithelial-mesenchymal transition and invasion in vitro
Metrics: PDF 1501 views | HTML 2114 views | ?
Shaopeng Chen1, Ying Tan1, Haihua Deng4, Zhifa Shen3, Yanhong Liu1, Pan Wu1, Chunyan Tan1 and Yuyang Jiang1,2
1Graduate School at Shenzhen, Tsinghua University, Shenzhen 518055, China
2School of Pharmaceutical Sciences, Tsinghua University, Beijing, 100084, P. R. China
3Key Laboratory of Laboratory Medicine, Ministry of Education of China, Zhejiang Provincial Key Laboratory of Medical Genetics, School of Laboratory Medicine and Life Sciences, Wenzhou Medical University, Wenzhou 325035, China
4Fuyong Hospital, Shenzhen, 518055, China
Chunyan Tan, email: [email protected]
Yuyang Jiang, email: [email protected]
Keywords: hepatocellular carcinoma, UBE2J2, epithelial-mesenchymal transition, EGFR, invasion
Received: December 20, 2016 Accepted: April 12, 2017 Published: May 03, 2017
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.
All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 3.0 License.