title: CrkL meditates CCL20/CCR6-induced EMT in gastric cancer.
abstract: BACKGROUND
  In recent years, Crk-like adapter protein (CrkL) has been identified as a key regulator in the epithelial-to-mesenchymal transition (EMT). However, the molecular mechanisms underlying the CC chemokine receptor 6 (CCR6) and chemokine (C-C motif) ligand 20 (CCL20)-induced EMT in gastric cancer are still unclear.
  
  
  METHODS
  We conducted the immunohistochemistry and immunoblotting to detect the expression of CCR6 and CrkL in 90 cases of gastric cancer tissues and five kinds of cell lines. And then, gastric cancer cells were subjected to small interfering RNA (siRNA) treatment and in vitro assay.
  
  
  RESULTS
  Both CCR6 and CrkL were aberrantly expressed in gastric cancer specimens and closely correlated with differentiation of cell lines. The expression of CCR6 and CrkL was also significantly associated with metastasis, stage, and poor prognosis of gastric cancer. In addition, we validated CCL20 activated the expression of p-CrkL, p-Erk1/2, p-Akt, vimentin, N-cadherin and MMP2 in MGC803 cells in a dose-dependent manner. However, si-CrkL abrogated the CCL20-induced p-Erk1/2, vimentin, N-cadherin and MMP2 expression. Most importantly, the knockdown of CrkL decreased migration and invasion of MGC803 cells.
  
  
  CONCLUSIONS
  CrkL mediates CCL20/CCR6-induced EMT via Akt pathway, instead of Erk1/2 pathway in development of gastric cancer, which indicated CCL20/CCR6-CrkL-Erk1/2-EMT pathway may be targeted to antagonize the progression of gastric cancer.
authors.affiliation: Department of General Surgery, Affiliated Hospital of Shandong Academy of Medical Sciences, Jinan, Shandong, China.
authors.forename: Gang
authors.initials: G
authors.lastname: Han
authors.affiliation: Department of General Surgery, Huimin County Hospital of Shandong Province, Binzhou, Shandong, China.
authors.forename: Dawei
authors.initials: D
authors.lastname: Wu
authors.affiliation: Department of General Surgery, Huimin County Hospital of Shandong Province, Binzhou, Shandong, China.
authors.forename: Yongan
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Department of General Surgery, Affiliated Hospital of Shandong Academy of Medical Sciences, Jinan, Shandong, China.
authors.forename: Zhiyun
authors.initials: Z
authors.lastname: Li
authors.affiliation: Department of General Surgery, Huimin County Hospital of Shandong Province, Binzhou, Shandong, China.
authors.forename: Jiapin
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of General Surgery, Affiliated Hospital of Shandong Academy of Medical Sciences, Jinan, Shandong, China. Electronic address: lichengjunsdma@163.com.
authors.forename: Chengjun
authors.initials: C
authors.lastname: Li
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D000368:Aged; D015820:Cadherins / Q000235:genetics / Q000378:metabolism; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D054418:Chemokine CCL20 / Q000502:physiology*; D058750:Epithelial-Mesenchymal Transition; D005260:Female; D005500:Follow-Up Studies; D055785:Gene Knockdown Techniques; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D008875:Middle Aged; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D009687:Nuclear Proteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D051058:Oncogene Protein v-akt / Q000378:metabolism; D011379:Prognosis; D034741:RNA, Small Interfering / Q000235:genetics; D054399:Receptors, CCR6 / Q000502:physiology*; D015398:Signal Transduction; D013274:Stomach Neoplasms / Q000276:immunology / Q000473:pathology* / Q000503:physiopathology*; D014746:Vimentin / Q000378:metabolism
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C108355:CCL20 protein, human; C082869:CRKL protein; D015820:Cadherins; D054418:Chemokine CCL20; D009687:Nuclear Proteins; D034741:RNA, Small Interfering; D054399:Receptors, CCR6; D014746:Vimentin; D051058:Oncogene Protein v-akt; D048052:Mitogen-Activated Protein Kinase 3; D020778:Matrix Metalloproteinase 2
keywords: CCL20/CCR6; CrkL; EMT; Erk1/2; Gastric cancer