Department of Biochemistry and Molecular Biology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, PR China.
Oncol Rep. 2012 Nov;28(5):1709-18. doi: 10.3892/or.2012.2003. Epub 2012 Aug 30.
A disintegrin and metalloproteinase 10 (ADAM10) was identified as a key protease in the ectodomain shedding of various substrates, such as Notch1 protein, ErbB2 and E-cadherin, which are important in the development of non-small cell lung cancer (NSCLC). The aim of this study was to investi-gate the role of ADAM10 in NSCLC metastasis.We characterized the expression of ADAM10 and Notch1 in human NSCLC tissues in vivo. Immunohistochemical analysis indicated that ADAM10 expression was significantly increased in the NSCLC tissues, particularly in the metastatic tissues. Futhermore, ADAM10 overexpression positively correlated with Notch1 expression in the NSCLC tissues. The in vitro downregulation of ADAM10 expression using ADAM10 short hairpin RNA (shRNA) reduced the migration and invasion of NSCLC cells. We present further evidence that ADAM10 promotes NSCLC cell migration and invasion via the activation of the Notch1 signaling pathway. Taken together, our results suggest that ADAM10 may serve as a potential target for the therapeutic intervention of NSCLC metastasis. The data provided in this study may aid in the further understanding of the function of ADAM10 in the progression of NSCLC and open new perspectives for the diagnosis and treatment of NSCLC.
解整合素金属蛋白酶 10（ADAM10）被鉴定为各种底物的外显域脱落的关键蛋白酶，这些底物如 Notch1 蛋白、ErbB2 和 E-钙黏蛋白，在非小细胞肺癌（NSCLC）的发展中非常重要。本研究旨在研究 ADAM10 在 NSCLC 转移中的作用。我们在体内对人类 NSCLC 组织中 ADAM10 和 Notch1 的表达进行了表征。免疫组织化学分析表明，ADAM10 在 NSCLC 组织中表达显著增加，特别是在转移性组织中。此外，ADAM10 的过表达与 NSCLC 组织中 Notch1 的表达呈正相关。使用 ADAM10 短发夹 RNA（shRNA）下调 ADAM10 表达可减少 NSCLC 细胞的迁移和侵袭。我们提供了进一步的证据表明，ADAM10 通过激活 Notch1 信号通路促进 NSCLC 细胞的迁移和侵袭。综上所述，我们的研究结果表明，ADAM10 可能成为 NSCLC 转移治疗干预的潜在靶点。本研究提供的数据可能有助于进一步了解 ADAM10 在 NSCLC 进展中的功能，并为 NSCLC 的诊断和治疗开辟新的视角。
