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UBE2C Induces EMT Through Wnt/β‑catenin and PI3K/Akt Signaling Pathways by Regulating Phosphorylation Levels of Aurora-A

Overview
Journal Int J Oncol
Specialty Oncology
Date 2017 Mar 6
PMID 28260026
Citations 39
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Abstract

The ubiquitin-conjugating enzyme 2C (UBE2C) is the key component in the ubiquitin proteasome system (UPS) by partnering with the anaphase‑promoting complex (APC/C). A high UBE2C protein expression level has been reported in various types of human tumors. However, little is known about the precise mechanism by which UBE2C expression is downregulated in gastric cancer. We found in MGC‑803 and SGC‑7901 gastric cancer cells UBE2C‑deficient G2/M phase arrest in the cell cycle and subsequently decreased gastric adenocarcinoma tumorigenesis. In the previous study, we identified Aurora-A (AURKA) as the hub gene of the gastric cancer linkage network based genome‑wide association study (eGWAS). Furthermore, knockdown of UBE2C using siRNA markedly reduced the level of phosphorylation AURKA (p‑AURKA) via Wnt/β‑catenin and PI3K/Akt signaling pathways suppressed the occurrence and development of gastric cancer. Additionally, the expression of E‑cadherin was up‑regulated and N-cadherin was downregulated in response to UBE2C knockdown and inhibits epithelial-mesenchymal transition (EMT). Collectively, our data suggest that the activity of AURKA might be regulated by UBE2C through regulating the activity of APC/C. UBE2C may be a new marker in the diagnosis of gastric cancer and may be a potential therapeutic target for the treatment of gastric adenocarcinoma.

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References
1.
Ferlay J, Soerjomataram I, Dikshit R, Eser S, Mathers C, Rebelo M . Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer. 2014; 136(5):E359-86. DOI: 10.1002/ijc.29210. View

2.
Wing S, Jain P . Molecular cloning, expression and characterization of a ubiquitin conjugation enzyme (E2(17)kB) highly expressed in rat testis. Biochem J. 1995; 305 ( Pt 1):125-32. PMC: 1136439. DOI: 10.1042/bj3050125. View

3.
Radice G . N-cadherin-mediated adhesion and signaling from development to disease: lessons from mice. Prog Mol Biol Transl Sci. 2013; 116:263-89. PMC: 6047516. DOI: 10.1016/B978-0-12-394311-8.00012-1. View

4.
Yang L . Incidence and mortality of gastric cancer in China. World J Gastroenterol. 2006; 12(1):17-20. PMC: 4077485. DOI: 10.3748/wjg.v12.i1.17. View

5.
Gheldof A, Berx G . Cadherins and epithelial-to-mesenchymal transition. Prog Mol Biol Transl Sci. 2013; 116:317-36. DOI: 10.1016/B978-0-12-394311-8.00014-5. View