Abstract
BackgroundsEmerging evidence has demonstrated that WISP2 is critically involved in cell proliferation, migration, invasion and metastasis in cancers. However, the function of WISP2 in esophageal squamous cell carcinoma (ESCC) is largely unclear. Therefore, we aim to explore the effects and the potential mechanism of WISP2 on proliferation and motility and invasion of ESCC cells.MethodsCell proliferation was detected by MTT assay and apoptosis was measured by FACS in ESCC cells after WISP2 downregulation and overexpression. Cell migration and invasion were analyzed by wound healing assay and transwell migration assay, respectively. The expression of ERK-1/2, Slug and E-cadherin was measured by Western blot respectively. IHC was performed to measure the expression of WISP2 in ESCC tissues.ResultsWISP2 overexpression is associated with survival in ESCC patients. WISP2 overexpression inhibited cell growth and induced cell apoptosis, suppressed cell migration and invasion in ESCC cells. Moreover, WISP overexpression retarded tumor growth in mouse model. WISP2 downregulation enhanced cell growth, inhibited apoptosis, promoted cell migration and invasion in ESCC cells. Mechanistically, WISP2 exerts its tumor suppressive functions via regulation of ERK1/2, Slug, and E-cadherin in ESCC cells.ConclusionsOur findings suggest that activation of WISP2 could be a useful therapeutic strategy for the treatment of ESCC.
Highlights
Esophageal cancer is the common malignant neoplasm, which arises from the mucosa or gland of the esophagus
Expression of WNT1 inducible signaling pathway protein 2 (WISP2) is associated with clinical significance in esophageal squamous cell carcinoma (ESCC) To explore the association of WISP2 and clinicopathologic significance in ESCC, we measured the protein of WISP2 in 216 cases of ESCC and 60 cases of normal esophageal epithelium by immunohistochemistry method (Table 1)
We found that the positive expression rate of WISP2 protein was 35.65% (77/216) in 216 cases of ESCC tissues. 64.35% tumor tissues have negative expression of WISP2, suggesting that lower expression of WISP2 was exhibited in ESCC tissues. 51.66% of positive expression of WISP2 in 60 cases of esophageal normal mucosa was observed (Table 2)
Summary
Esophageal cancer is the common malignant neoplasm, which arises from the mucosa or gland of the esophagus. WISP2 waas reported to have higher expression in breast cancer patients at late stages with metastasis, indicating that WISP2 plays an oncogenic role in breast cancer [9]. WISP2 expression is associated with tumor stage, differentiation status, and overall survival [13]. Another group reported that WISP2 was highly expressed in gastric tissues compared to adjacent normal tissues [14]. It has been reported that lower WISP2 expression was observed in pancreatic cancer tissues [15] These studies indicated that WISP2 plays an important role in the development and progression of human cancers
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