title: Alpha-actinin 4 is associated with cancer cell motility and is a potential biomarker in non-small cell lung cancer.
abstract: BACKGROUND
  Differential expression and secretion of alpha-actinin 4 (ACTN4) in the lung cancer cell lines CL1-0 and CL1-5 have been reported in previous proteomic studies. The aim of this study is to investigate the functional properties of the ACTN4 protein in non-small-cell lung cancer (NSCLC) cells and evaluate its clinical importance.
  
  
  METHODS
  We used RNA interference to knock down and overexpress ACTN4 protein to evaluate the effects of this intervention on cancer cell invasion and migration, as well as on microscopic cellular morphology. Furthermore, we examined by immunohistochemistry the expression of ACTN4 protein in tissue samples at different stages of lung cancer and compared the protein levels of ACTN4 in blood plasma samples from patients with histologically confirmed lung cancer and healthy controls.
  
  
  RESULTS
  CL1-5 cell motility was significantly suppressed by the knockdown of ACTN4 protein. The morphology of CL1-5 cells changed from a predominantly mesenchymal-like shape into a globular shape in response to ACTN4 protein knockdown. A quantitative immunohistochemical assessment of lung cancer tissues revealed that ACTN4 protein level was considerably higher in cancerous tissues than in the adjacent normal ones, and the area under the receiver operating characteristic curve was 0.736 (p < 0.001). According to an enzyme-linked immunosorbent assay, the plasma levels of ACTN4 protein were significantly different between cancer patients and healthy controls, and the areas under the receiver operating characteristic curves were 0.828 and 0.909, respectively, for two independent cohorts (p < 0.001).
  
  
  CONCLUSIONS
  We demonstrate that the knockdown of ACTN4 protein inhibited cell invasion and migration. These results suggest that ACTN4 is associated with lung cancer cell motility. Thus, the level of ACTN4 in cancerous tissue and plasma is related to the presence of lung cancer.
authors.affiliation: *Department of Environmental and Occupational Health, College of Medicine, National Cheng Kung University, 138 Sheng-Li Road, Tainan 704, Taiwan. †Department of Medical Imaging and Radiological Sciences, Kaohsiung Medical University, 100 Shi-Chuan 1st Road, Kaohsiung 807, Taiwan. ‡Translational Research Center, Kaohsiung Medical University Hospital, 100 Tzyou 1st Road, Kaohsiung 807, Taiwan. §Institute of Medical Science and Technology, National Sun Yat-Sen University, 70 Lienhai Road, Kaohsiung 804, Taiwan. ║Division of Thoracic Surgery, Kaohsing Veterans General Hospital, 386 Ta-Chung 1st RD. Kaohsiung 813, Taiwan. ¶Department of Surgery, College of Medicine, National Cheng Kung University Hospital, National Cheng Kung University, 138 Sheng-Li Road, Tainan 704, Taiwan. #Department of Internal Medicine, College of Medicine, National Cheng Kung University Hospital, National Cheng Kung University, 138 Sheng-Li Road, Tainan 704, Taiwan.
authors.forename: Ming-Chuan
authors.initials: MC
authors.lastname: Wang
authors.forename: Ying-Hua
authors.initials: YH
authors.lastname: Chang
authors.forename: Chih-Chieh
authors.initials: CC
authors.lastname: Wu
authors.forename: Yu-Chang
authors.initials: YC
authors.lastname: Tyan
authors.forename: Hua-Chien
authors.initials: HC
authors.lastname: Chang
authors.forename: Yih-Gang
authors.initials: YG
authors.lastname: Goan
authors.forename: Wu-Wei
authors.initials: WW
authors.lastname: Lai
authors.forename: Pin-Nan
authors.initials: PN
authors.lastname: Cheng
authors.forename: Pao-Chi
authors.initials: PC
authors.lastname: Liao
mesh_terms: D000185:Actinin / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D016022:Case-Control Studies; D048708:Cell Growth Processes / Q000502:physiology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000502:physiology*; D055785:Gene Knockdown Techniques; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D034741:RNA, Small Interfering / Q000008:administration & dosage / Q000235:genetics; D014162:Transfection
chemical_list: C111453:ACTN4 protein, human; D034741:RNA, Small Interfering; D000185:Actinin