title: Overexpression of MUC1 enhances proangiogenic activity of non-small-cell lung cancer cells through activation of Akt and extracellular signal-regulated kinase pathways.
abstract: BACKGROUND
  Angiogenesis is an important process required for tumor progression. Mucin 1 (MUC1) is a transmembrane glycoprotein that is aberrantly upregulated in many types of cancer, including non-small-cell lung cancer (NSCLC). However, the biological significance of MUC1 overexpression in lung cancer angiogenesis is not completely understood.
  
  
  METHODS
  We showed that enforced expression of MUC1 in two NSCLC cell lines, A549 and NCI-H460, which have a low level of endogenous MUC1, promoted their ability to induce vascular endothelial growth factor (VEGF)-dependent endothelial cell migration and tube formation.
  
  
  RESULTS
  There was a significant increase in VEGF expression in MUC1-overexpressing NSCLC cells. Moreover, MUC1 overexpression resulted in a marked elevation in phosphorylated Akt and extracellular signal-regulated kinase (ERK)1/2, indicative of activation of both signaling pathways. Most importantly, inhibition of Akt or ERK signaling using specific chemical inhibitors restrained the proangiogenic activity of MUC1-overexpressing NSCLC cells.
  
  
  CONCLUSIONS
  Taken together, our present data demonstrate that the aberrant upregulation of MUC1 favors tumor angiogenesis in NSCLC, likely through the activation of both Akt and ERK pathways and elevation of VEGF production. MUC1 may thus be a potential antiangiogenic target in NSCLC.
authors.affiliation: Department of Severe Respiratory, First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
authors.forename: Mengying
authors.initials: M
authors.lastname: Yao
authors.forename: Weihong
authors.initials: W
authors.lastname: Zhang
authors.forename: Qingxian
authors.initials: Q
authors.lastname: Zhang
authors.forename: Lihua
authors.initials: L
authors.lastname: Xing
authors.forename: Aiguo
authors.initials: A
authors.lastname: Xu
authors.forename: Qiuhong
authors.initials: Q
authors.lastname: Liu
authors.forename: Bing
authors.initials: B
authors.lastname: Cui
mesh_terms: D002289:Carcinoma, Non-Small-Cell Lung / Q000098:blood supply / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement; D004730:Endothelium, Vascular / Q000378:metabolism / Q000473:pathology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008175:Lung Neoplasms / Q000098:blood supply / Q000378:metabolism* / Q000473:pathology; D020935:MAP Kinase Signaling System / Q000502:physiology*; D018396:Mucin-1 / Q000378:metabolism*; D009389:Neovascularization, Pathologic / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology; D015854:Up-Regulation; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: C060192:MUC1 protein, human; D018396:Mucin-1; D042461:Vascular Endothelial Growth Factor A; D051057:Proto-Oncogene Proteins c-akt; D048049:Extracellular Signal-Regulated MAP Kinases