Department of General Surgery, The people's hospital of Suzhou National New &Hi-Tec Industrial development Zone, Suzhou, 215129, Jiangsu, P. R. China.
Department of Biliary-Pancreatic Surgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, 1630 Dongfang Road, Shanghai, 200127, P. R. China.
Sci Rep. 2018 Oct 25;8(1):15792. doi: 10.1038/s41598-018-34094-3.
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.
由于治疗耐药和频繁转移,胰腺导管腺癌(PDAC)仍然是最恶性的癌之一。WNT7A 是 Wnt/β-catenin 信号通路的重要配体,在肿瘤发展中具有争议的作用。WNT7A 在 PDAC 中的作用尚不清楚。在这项研究中,我们分析了 WNT7A 在 mRNA 和蛋白水平的表达模式。我们发现与相邻的非肿瘤组织相比,胰腺癌组织显示出显著高的 WNT7A 表达,并且 WNT7A 的表达与不良预后和淋巴结转移呈正相关。然后,我们在体外进行了 Transwell 测定和划痕愈合测定,发现 WNT7A 促进了癌细胞的迁移能力。此外,我们探讨了 WNT7A 诱导细胞迁移的潜在机制。结果表明,上调的 WNT7A 表达诱导 N-钙黏蛋白表达升高和 E-钙黏蛋白表达降低,而在 WNT7A 敲低组中则出现相反的结果,这表明 WNT7A 可能有助于上皮-间充质转化。最后,我们发现缺氧培养条件显著增加了 WNT7A 的表达。总之,我们的工作表明,缺氧诱导的 WNT7A 高表达可能通过增强 PDAC 中的上皮-间充质转化来促进细胞迁移。