title: Trim44 facilitates the migration and invasion of human lung cancer cells via the NF-κB signaling pathway.
abstract: BACKGROUND
  Trim44 is an important member of the tripartite motif-containing protein (TRIM) family. Recent research reported that Trim44 might play an important role in tumorigenesis, although its role in non-small cell lung cancer (NSCLC) and the related mechanisms is not yet known.
  
  
  METHODS
  In this study we analyzed 30 pairs of NSCLC tumors and the matched adjacent normal tissue to define the relationship between Trim44 and NSCLC tumors. The function of Trim44 in cell migration and invasion was determined by overexpression of Trim44 in normal bronchial epithelial cell line 16HE or knockdown of Trim44 in A549 cells, respectively. Whether Trim44-mediated NF-κB signaling activation was involved in Trim44-mediated promotion of lung cancer was tested by q-PCR analysis and cell migration and invasion assay using PDTC, an inhibitor of NF-κB.
  
  
  RESULTS
  We found that Trim44 was upregulated in NSCLC tumors (14/30 cases; 46.7%). Furthermore, Trim44 was upregulated in many NSCLC cell lines, especially in A549 and H441. Moreover, Trim44 significantly enhanced cell migration and invasion ability, which was related to increased CXCR6 and matrix metalloproteinase 9 (MMP9). Knockdown of Trim44 in A549 cells by siRNA showed a diminished effect in cell migration and invasion. Further investigation revealed that blocking the NF-κB signaling pathway using PDTC, an inhibitor of NF-κB, reversed the expression of CXCR6 and MMP9, and alleviated the promotion of migration and invasion mediated by Trim44.
  
  
  CONCLUSIONS
  Our data suggest that Trim44 promotes NSCLC development through activation of NF-κB signaling via upregulating CXCL16 and MMP9 expression.
authors.affiliation: Nanjing Medical University, Nanjing, 210029, China.
authors.forename: Qingquan
authors.initials: Q
authors.lastname: Luo
authors.forename: Hao
authors.initials: H
authors.lastname: Lin
authors.forename: Xiangyun
authors.initials: X
authors.lastname: Ye
authors.forename: Jia
authors.initials: J
authors.lastname: Huang
authors.forename: Shun
authors.initials: S
authors.lastname: Lu
authors.forename: Lin
authors.initials: L
authors.lastname: Xu
mesh_terms: D002352:Carrier Proteins / Q000096:biosynthesis* / Q000235:genetics; D002465:Cell Movement; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis; D016328:NF-kappa B / Q000378:metabolism*; D009361:Neoplasm Invasiveness; D000075744:Receptors, CXCR6; D019707:Receptors, Chemokine / Q000096:biosynthesis; D011991:Receptors, Virus / Q000096:biosynthesis; D015398:Signal Transduction; D000070584:Tripartite Motif Proteins
chemical_list: C106330:CXCR6 protein, human; D002352:Carrier Proteins; D047908:Intracellular Signaling Peptides and Proteins; D016328:NF-kappa B; D000075744:Receptors, CXCR6; D019707:Receptors, Chemokine; D011991:Receptors, Virus; C540677:TRIM44 protein, human; D000070584:Tripartite Motif Proteins; C579270:MMP9 protein, human; D020780:Matrix Metalloproteinase 9