1 Shandong Provincial Key Laboratory of Radiation Oncology , Shandong Cancer Hospital and Institute, Jinan, The People's Republic of China .
Cancer Biother Radiopharm. 2012 Dec;27(10):672-7. doi: 10.1089/cbr.2012.1241. Epub 2012 Nov 9.
Lysyl oxidase (LOX), a copper-dependent amine oxidase known to function both intracellularly and extracellularly, is implicated in promoting tumor progression and hypoxic metastasis in certain malignancies. Nonsmall cell lung cancer (NSCLC) is a highly aggressive cancer with poor prognosis worldwide. However, the role and molecular mechanism by which LOX involving in hypoxic NSCLC invasion and migration are poorly understood. This study explores the effect of LOX on invasion and migration of NSCLC cells under hypoxic conditions. Small interfering RNA (siRNA) targeting LOX was used to silence LOX expression of hypoxic NSCLC cells, SPCA1 and A549. Cellular invasive and migratory potentials were determined by matrigel invasion and migration assays. Expression of LOX, Src, Src activation (Tyr418 phosphorylation of Src), and Snail were evaluated by real-time PCR and western blot, respectively. The results showed that LOX mRNA and protein expression were upregulated under hypoxic conditions in NSCLC cells. Knockdown of LOX led to inhibition of hypoxia-induced invasion and migration. Phosphorylated Src (Tyr418) and Snail proteins were decreased along with LOX downregulation. Our data provide molecular evidences that LOX is mechanistically linked to increased invasion and migration of hypoxic NSCLC cells, and may serve as an antimetastasis target of human NSCLC.
赖氨酰氧化酶（LOX）是一种铜依赖性胺氧化酶，已知其在细胞内和细胞外均具有功能，与某些恶性肿瘤的促进肿瘤进展和缺氧转移有关。非小细胞肺癌（NSCLC）是一种侵袭性强、预后差的癌症，在全球范围内都很常见。然而，LOX 参与缺氧 NSCLC 侵袭和迁移的作用和分子机制尚不清楚。本研究探讨了 LOX 在缺氧条件下对 NSCLC 细胞侵袭和迁移的影响。使用针对 LOX 的小干扰 RNA（siRNA）沉默缺氧 NSCLC 细胞 SPCA1 和 A549 中的 LOX 表达。通过基质胶侵袭和迁移实验测定细胞的侵袭和迁移潜能。通过实时 PCR 和 Western blot 分别评估 LOX、Src、Src 激活（Src 的 Tyr418 磷酸化）和 Snail 的表达。结果表明，在 NSCLC 细胞中，LOX mRNA 和蛋白表达在缺氧条件下上调。LOX 敲低导致缺氧诱导的侵袭和迁移受到抑制。随着 LOX 下调，磷酸化 Src（Tyr418）和 Snail 蛋白减少。我们的数据提供了分子证据，表明 LOX 与缺氧 NSCLC 细胞侵袭和迁移的增加在机制上有关，并且可能成为人类 NSCLC 抗转移的靶点。
