Angiopoietin-like protein 1 suppresses SLUG to inhibit cancer cell motility
Angiopoietin-like protein 1 suppresses SLUG to inhibit cancer cell motility
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DOI：
10.1172/jci64044
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发表时间：
2013-03-01
影响因子：
15.9
通讯作者：
Kuo, Min-Liang
中科院分区：
文献类型：
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作者：
Kuo, Tsang-Chih;Tan, Ching-Ting;Kuo, Min-Liang
血管生成素样蛋白1（ANGPTL 1）是一种有效的血管生成调节因子。越来越多的证据表明，ANGPTL家族蛋白不仅靶向内皮细胞，而且影响肿瘤细胞的行为。在102例肺癌患者的筛查中，我们发现ANGPTL 1表达与浸润、淋巴结转移和不良临床结局呈负相关。ANGPTL 1在体外抑制肺癌和乳腺癌细胞系的迁移、侵袭和转移能力，并减少注射过表达ANGPTL 1的癌细胞系的小鼠的转移。ANGPTL 1的异位表达通过减少锌指蛋白SLUG的表达来抑制上皮向间质转化（EMT）。microRNA筛选显示，ANGPTL 1通过以整合素α（1）β（1）/FAK/ERK/SP1途径依赖性方式诱导miR-630表达来抑制SLUG。这些结果表明，ANGPTL 1通过消除EMT介体SLUG的表达来抑制肺癌细胞运动。
Angiopoietin-like protein 1 (ANGPTL1) is a potent regulator of angiogenesis. Growing evidence suggests that ANGPTL family proteins not only target endothelial cells but also affect tumor cell behavior. In a screen of 102 patients with lung cancer, we found that ANGPTL1 expression was inversely correlated with invasion, lymph node metastasis, and poor clinical outcomes. ANGPTL1 suppressed the migratory, invasive, and metastatic capabilities of lung and breast cancer cell lines in vitro and reduced metastasis in mice injected with cancer cell lines overexpressing ANGPTL1. Ectopic expression of ANGPTL1 suppressed the epithelial-to-mesenchymal transition (EMT) by reducing the expression of the zinc-finger protein SLUG. A microRNA screen revealed that ANGPTL1 suppressed SLUG by inducing expression of miR-630 in an integrin alpha(1)beta(1)/FAK/ERK/SP1 pathway-dependent manner. These results demonstrate that ANGPTL1 represses lung cancer cell motility by abrogating the expression of the EMT mediator SLUG.