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.
journal_name
Mol Med Repjournal_title
Molecular medicine reportsauthors
Tian P,Liu D,Sun L,Sun Hdoi
10.3892/mmr.2018.8503subject
Has Abstractpub_date
2018-04-01 00:00:00pages
5362-5367issue
4eissn
1791-2997issn
1791-3004journal_volume
17pub_type
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