Proteasome inhibitor MG132 suppresses pancreatic ductal adenocarcinoma‑cell migration by increasing ESE3 expression

Jin,Fanjie; Xiao,Di; Zhao,Tiansuo; Yu,Ming

doi:10.3892/ol.2019.11157

Proteasome inhibitor MG132 suppresses pancreatic ductal adenocarcinoma‑cell migration by increasing ESE3 expression

Authors:
- Fanjie Jin
- Di Xiao
- Tiansuo Zhao
- Ming Yu
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Affiliations: Department of Pancreatic Cancer, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin 300060, P.R. China, Department of Nutrition and Food Science, School of Public Health, Tianjin Medical University, Tianjin 300070, P.R. China
Published online on: November 28, 2019 https://doi.org/10.3892/ol.2019.11157
Pages: 858-868
Copyright: © Jin et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

The clinical significance of the proteasome inhibitor MG132 has been examined in numerous human cancer types; however, its influence on the metastasis and progression of pancreatic cancer is yet to be determined. In the present study, the effect of MG132 treatment on pancreatic ductal adenocarcinoma (PDAC) cell lines (SW1990 and PANC‑1) was examined. Compared with the control groups, MG132 treatment resulted in higher expression levels of ETS homologous factor (ESE3), a crucial member of the E26 transformation‑specific family that is central to various differentiation and development processes in epithelial tissues. MG132 treatment also increased the nuclear translocation of ESE3. Mechanistically, MG132 further inhibited the invasion and migration of PDAC cells by promoting E‑cadherin expression, which not only plays an important role in cell‑cell adhesion, but is also a direct target of ESE3. Furthermore, subsequent knockdown experiments, using short interfering RNAs, demonstrated that MG132 upregulated E‑cadherin via an increase in ESE3 expression. The results of the present study support the hypothesis that MG132 treatment inhibits PDAC metastasis, highlighting the potential of MG132 as a therapeutic agent for the treatment of patients with PDAC.

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