Abstract
Due to the therapy resistance and frequent metastasis, pancreatic ductal adenocarcinoma(PDAC) remains one of the most malignant carcinoma. WNT7A, an important ligand of Wnt/β-catenin signaling pathways, has a controversial role in tumor development. The role of WNT7A in PDAC remains unclear. In this study, we analyzed the expression pattern of WNT7A at mRNA and protein levels. We found pancreatic cancer tissue demonstrated a significant high WNT7A expression compared with the adjacent non-tumor tissue and the expression of WNT7A positively correlates with poor prognosis and lymph node metastasis. Then, we performed transwell assays and wound healing assays in vitro and found that WNT7A promotes the migration capacity of cancer cells. Furthermore, we explored the underlying mechanism of the WNT7A inducing cell migration. Results showed that up-regulated WNT7A expression inducing higher expression of N-cadherin and lower expression of E-cadherin while the contrast result was shown in the WNT7A knock-down group, which suggested that WNT7A might contribute to an epithelial–mesenchymal transition. Finally, we found that the hypoxia culture condition remarkably increased the WNT7A expression. In conclusion, our work demonstrated that hypoxia induced high expression of WNT7A might promote the cell migration via enhancing the epithelial–mesenchymal transition in PDAC.
Highlights
Pancreatic ductal adenocarcinoma remains one of the most lethal malignancies with frequent metastasis and recurrence[1]
We found that WNT7A expression dramatically increased in PDAC tissue compared with paired adjacent non-tumor tissue in GSE16515(p = 0.0399) and GSE28735(p = 0.0091)
The results suggested that WNT7A is remarkably increased in PDAC tissue compared to adjacent non-tumor tissue (p = 0.0091)
Summary
Pancreatic ductal adenocarcinoma remains one of the most lethal malignancies with frequent metastasis and recurrence[1]. Despite the relative low incidence, PDAC is the fourth cause of cancer-related deaths in developed countries with a 5-year survival rate of only 8.2%2. The survival rate for PDAC patients stays almost unchanged for more than 40 years[3]. One of the main reasons causing extremely low survival rate of PDAC is that most patients are diagnosed with metastasis and are ineligible for curative surgical resection. Over the years evidence is accumulated indicate that EMT is a vital step for malignance related metastasis[5,6]. Various Pathways regulating EMT including HGF, EGF,TGF-β, Notch, and Wnt/β-catenin signaling pathways[5]. The role of WNT7A in Pancreatic ductal adenocarcinoma remains unclear. We investigated the roles of WNT7A in PDAC and explore the possible mechanism involved in WNT7A-mediated functions
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