Cullin7 promotes epithelial‑mesenchymal transition of esophageal carcinoma via the ERK‑SNAI2 signaling pathway

Tian,Ping; Liu,Dandan; Sun,Luyi; Sun,Hui

doi:10.3892/mmr.2018.8503

Cullin7 promotes epithelial‑mesenchymal transition of esophageal carcinoma via the ERK‑SNAI2 signaling pathway

Authors:
- Ping Tian
- Dandan Liu
- Luyi Sun
- Hui Sun
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Affiliations: Department of Gastroenterology, Yidu Central Hospital of Weifang, Weifang, Shandong 262500, P.R. China, Department of Radiotherapy, Yidu Central Hospital of Weifang, Weifang, Shandong 262500, P.R. China, Department of Surgical Oncology, Weifang People's Hospital, Weifang, Shandong 261041, P.R. China
Published online on: January 26, 2018 https://doi.org/10.3892/mmr.2018.8503
Pages: 5362-5367

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Abstract

Cullin7 (CUL7) is a member of Cullin protein family and exhibits a tumor‑promoting role in several types of tumors, including breast, liver and ovarian. However, its roles in esophageal carcinoma (EC) have not yet been reported. In the present study, CUL7 expression in EC tissue was revealed to be significantly higher compared with nontumoral tissues, as detected by immunohistochemistry (IHC; P=0.000). χ2 analysis confirmed that CUL7 expression was positively associated with invasion depth (P=0.000), lymph node involvement (P=0.033) and advanced clinical stage (P=0.000). Survival analysis demonstrated that CUL7 was positively associated with poor overall survival (P=0.001) and poor disease‑free survival (P=0.0019). An association of CUL7 with endothelial‑mesenchymal transition (EMT) was examined, and IHC results indicated that high CUL7 expression was associated with increased zinc finger protein SNAI2 (SNAI2) expression (P=0.000) and decreased E‑cadherin (P=0.000). Western blot analysis demonstrated that short hairpin RNA silencing CUL7 in EC1 cells increased epithelial (E)‑cadherin protein expression level, and decreased expression of Vimentin and SNAI2; cell migration was also reduced. Western blot analysis demonstrated that over expression of CUL7 in EC9706 cells increased Vimentin and SNAI2 protein expression, but decreased E‑cadherin expression, and the number of migratory cells. Investigation into the potential molecular mechanisms demonstrated that over expressing CUL7 in EC9706 cells stimulated the phosphorylation of ERK. Inhibiting ERK through treatment with U0126 significantly abrogated CUL7‑induced alterations in Vimentin, SNAI2 and E‑cadherin expression levels. Results from the present study demonstrated that CUL7 expression was associated with EC progression and poor prognosis. CUL7 may promote EMT via the ERK‑SNAI2 pathway in EC. These data may improve our understanding of the role of CUL7 in tumors and provide supporting evidence for the development of novel therapeutic targets for EC.

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