title: WNT5A/JNK signaling regulates pancreatic cancer cells migration by Phosphorylating Paxillin.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: School of Medicine, Nankai University, Tianjin 300071, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Wei
authors.forename: Hongyue
authors.initials: H
authors.lastname: Li
authors.forename: Na
authors.initials: N
authors.lastname: Li
authors.forename: Huihui
authors.initials: H
authors.lastname: Sun
authors.forename: Qiang
authors.initials: Q
authors.lastname: Li
authors.forename: Xiaohong
authors.initials: X
authors.lastname: Shen
mesh_terms: D000230:Adenocarcinoma / Q000503:physiopathology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects*; D006801:Humans; D048055:Mitogen-Activated Protein Kinase 8 / Q000096:biosynthesis / Q000502:physiology*; D010190:Pancreatic Neoplasms / Q000503:physiopathology*; D051419:Paxillin / Q000096:biosynthesis / Q000378:metabolism*; D010766:Phosphorylation; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*; D051153:Wnt Proteins / Q000096:biosynthesis / Q000502:physiology*; D000071818:Wnt-5a Protein
chemical_list: D051419:Paxillin; D011518:Proto-Oncogene Proteins; C085389:WNT5A protein, human; D051153:Wnt Proteins; D000071818:Wnt-5a Protein; D048055:Mitogen-Activated Protein Kinase 8
keywords: Migration; Pancreatic cancer cell; Paxillin; WNT5A/JNK signaling