Overexpression of MUC1 Enhances Proangiogenic Activity of Non-Small-Cell Lung Cancer Cells Through Activation of Akt and Extracellular Signal-regulated Kinase Pathways

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 can...

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Veröffentlicht in:Lung 2011-12, Vol.189 (6), p.453-460
Hauptverfasser: Yao, Mengying, Zhang, Weihong, Zhang, Qingxian, Xing, Lihua, Xu, Aiguo, Liu, Qiuhong, Cui, Bing
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Sprache:eng
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Zusammenfassung: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.
ISSN:0341-2040
1432-1750
DOI:10.1007/s00408-011-9327-y