High expression of WNT7A predicts poor prognosis and promote tumor metastasis in pancreatic ductal adenocarcinoma

• Published in: Scientific reports Vol. 8; no. 1; pp. 15792 - 10
• Main Authors: Wu, Dong-jin, Jiang, Yong-sheng, He, Rui-zhe, Tao, Ling-ye, Yang, Min-wei, Fu, Xue-liang, Yang, Jiang-yu, Zhu, Kun
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 25.10.2018; Nature Publishing Group; Nature Portfolio
• Subjects: 13/1; 13/105; 13/44; 13/51; 13/89; 14/63; 38; 38/109; 38/77; 631/67/395; 631/80/84; 82; 82/80; 96; Adenocarcinoma; Cell adhesion & migration; Cell culture; Cell migration; E-cadherin; Humanities and Social Sciences; Hypoxia; Lymph nodes; Mesenchyme; Metastases; Metastasis; mRNA; multidisciplinary; N-Cadherin; Pancreatic cancer; Pancreatic Ductal Adenocarcinoma (PDAC); PDAC Patients; PDAC Tissue; Performed Transwell Assays; Prognosis; Science; Science (multidisciplinary); Wnt protein; Wnt5a Expression; Wound healing; β-Catenin; Wnt5a Expression; PDAC Tissue; Performed Transwell Assays; Pancreatic Ductal Adenocarcinoma (PDAC); PDAC Patients
• DOI: 10.1038/s41598-018-34094-3
• ISSN: 2045-2322

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.