Department of Severe Respiratory, First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
Lung. 2011 Dec;189(6):453-60. doi: 10.1007/s00408-011-9327-y. Epub 2011 Oct 1.
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.
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.
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.
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.
血管生成是肿瘤进展所必需的重要过程。黏蛋白 1（MUC1）是一种跨膜糖蛋白，在许多类型的癌症中异常上调，包括非小细胞肺癌（NSCLC）。然而，MUC1 在肺癌血管生成中的过度表达的生物学意义尚不完全清楚。
我们表明，在两种 NSCLC 细胞系 A549 和 NCI-H460 中强制表达 MUC1，这两种细胞系内源性 MUC1 水平较低，促进了它们诱导血管内皮生长因子（VEGF）依赖性内皮细胞迁移和管状形成的能力。
在过表达 MUC1 的 NSCLC 细胞中，VEGF 表达显著增加。此外，MUC1 的过表达导致磷酸化 Akt 和细胞外信号调节激酶（ERK）1/2 的明显升高，表明两条信号通路均被激活。最重要的是，使用特异性化学抑制剂抑制 Akt 或 ERK 信号通路可限制过表达 MUC1 的 NSCLC 细胞的促血管生成活性。
综上所述，我们目前的数据表明，MUC1 的异常上调有利于 NSCLC 的肿瘤血管生成，可能通过激活 Akt 和 ERK 通路以及升高 VEGF 的产生。因此，MUC1 可能是 NSCLC 中的一种潜在的抗血管生成靶点。
