School of Medicine, Nankai University, Tianjin 300071, China.
Pancreatology. 2013 Jul-Aug;13(4):384-92. doi: 10.1016/j.pan.2013.05.008. Epub 2013 Jun 10.
Expression of WNT5A associated with aggressive tumor biology and poor clinical outcome of various types of cancer. However its function in the metastasis property of pancreatic cells still needs to be elucidated.
We detected the expressions of WNT5A, JNK1/p-JNK1 and Paxillin/p-Paxillin in cancer and the para-carcinoma tissues of pancreatic cancer. To understand how WNT5A/JNK signaling affects pancreatic cancer cell migration through the phosphorylation of cellular substrates of Paxillin, In vitro, we knocked down the WNT5A in PANC1, Capan-2 and HT1080 cell lines, and then tested the expression of JNK1. We detected the proteins of phosphorylation of Paxillin after JNK1 was inhibited and then the cells migration assay was evaluated. Moreover, JNK1 functionally phosphorylates serine178 on paxillin in vitro was detected .At last we subsequently observed whether WNT5A/JNK signaling modulates some molecule expressions relevant to focal adhesion (FA) formation and mesenchymal transition (EMT) and cell cycle.
WNT5A, p-JNK1 and p-Paxillin were highly expressed in early stage of tumor tissues. In vitro, WNT5A/JNK signaling promotes cell migration in pancreatic cancer by phosphorylating serine178 on Paxillin, an FA adaptor, which means WNT5A may regulate FA's function.WNT5A up-regulates the molecule's expressions relevant to cell adhesion through the phosphorylation of JNK1, including MMP1, MMP2, ICAM and CD44. In addition, WNT5A/JNK signaling promoted the mRNA expressions of vimentin, but decreased in E-Cadherin expression, which suggested its regulatory effects on the EMT processes. WNT5A/JNK signaling didn't modulate cell proliferation.
WNT5A/JNK signaling initiate cell migration of pancreatic cancer through activation of Paxillin, which suggested WNT5A has the potency of being an effective therapeutic target for the metastasis of pancreatic cancer.
WNT5A 的表达与各种癌症的侵袭性肿瘤生物学和不良临床结局相关。然而，其在胰腺细胞转移特性中的功能仍有待阐明。
我们检测了癌症和胰腺癌旁组织中 WNT5A、JNK1/p-JNK1 和 Paxillin/p-Paxillin 的表达。为了了解 WNT5A/JNK 信号如何通过磷酸化 Paxillin 的细胞底物来影响胰腺癌细胞迁移，我们在体外敲低了 PANC1、Capan-2 和 HT1080 细胞系中的 WNT5A，然后检测了 JNK1 的表达。我们检测了 JNK1 被抑制后 Paxillin 磷酸化的蛋白表达，然后评估了细胞迁移实验。此外，还检测了 JNK1 在体外对 Paxillin 丝氨酸 178 的功能性磷酸化。最后，我们观察了 WNT5A/JNK 信号是否调节与粘着斑（FA）形成和间质转化（EMT）和细胞周期相关的一些分子的表达。
WNT5A、p-JNK1 和 p-Paxillin 在肿瘤组织的早期高表达。在体外，WNT5A/JNK 信号通过磷酸化粘着斑（FA）衔接蛋白 Paxillin 的丝氨酸 178 促进胰腺癌细胞迁移，这意味着 WNT5A 可能调节 FA 的功能。WNT5A 通过磷酸化 JNK1 上调与细胞黏附相关的分子表达，包括 MMP1、MMP2、ICAM 和 CD44。此外，WNT5A/JNK 信号促进了波形蛋白的 mRNA 表达，但降低了 E-钙黏蛋白的表达，这表明其对 EMT 过程的调节作用。WNT5A/JNK 信号不调节细胞增殖。
WNT5A/JNK 信号通过激活 Paxillin 启动胰腺癌细胞迁移，这表明 WNT5A 具有成为胰腺癌细胞转移的有效治疗靶点的潜力。
