Leucine aminopeptidase 3 promotes migration and invasion of breast cancer cells through upregulation of fascin and matrix metalloproteinases-2/9 expression
Leucine aminopeptidase 3 promotes migration and invasion of breast cancer cells through upregulation of fascin and matrix metalloproteinases-2/9 expression
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亮氨酸氨肽酶 3 通过上调肌成束蛋白和基质金属蛋白酶-2/9 的表达来促进乳腺癌细胞的迁移和侵袭。
DOI：
10.1002/jcb.27638
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发表时间：
2019-03-01
影响因子：
4
通讯作者：
Wang, Xuejian
中科院分区：
文献类型：
--
作者：
Fang, Chunyan;Zhang, Jian;Wang, Xuejian
亮氨酸氨基肽酶3 （leucine aminopeptidase 3, LAP3）的过表达参与了多种肿瘤细胞的增殖、迁移和侵袭，在肿瘤转移中起着至关重要的作用。然而，相关机制尚不清楚。在本研究中，我们利用MDA-MB-231和MCF7乳腺癌细胞系，利用天然LAP3抑制剂bestatin和过表达或敲除LAP3的慢病毒载体，探索LAP3在调节癌细胞迁移和侵袭中的作用。贝司他汀抑制肿瘤细胞的迁移和侵袭呈剂量依赖性。Western blot结果显示，bestatin和敲低LAP3上调了Hsp27的磷酸化，下调了fascin的表达。Akt磷酸化和基质金属蛋白酶2/9的表达也下调。LAP3过表达的结果与此相反。采用免疫组化方法检测乳腺癌组织中LAP3的表达水平。LAP3高表达与肿瘤的恶性程度相关。本研究结果揭示了LAP3在乳腺癌转移中的分子机制，提示LAP3可能作为潜在的抗转移治疗靶点。
Overexpression of leucine aminopeptidase 3 (LAP3) is involved in proliferation, migration, and invasion of several tumor cells and plays a crucial role in tumor metastasis. However, the related mechanism remains unknown. In this study, we used MDA-MB-231 and MCF7 breast cancer cell lines to explore the role of LAP3 in the regulation of cancer cell migration and invasion by employing the natural LAP3 inhibitor bestatin and a lentivirus vector that overexpresses or knocks down LAP3. Bestatin inhibited tumor cell migration and invasion in a dose-dependent manner. Western blot assay showed that bestatin and knockdown of LAP3 upregulated phosphorylation of Hsp27 and downregulated expression of fascin. Phosphorylation of Akt and expression of matrix metalloproteinase-2/9 can also be downregulated. LAP3 overexpression showed the opposite results. Immunohistochemistry analysis was conducted to detect expression levels of LAP3 in breast cancer tissues. High LAP3 expression was correlated with the grade of malignancy. Findings of this study uncovered the molecular mechanism of LAP3 on breast cancer metastasis and indicated that LAP3 may act as a potential antimetastasis therapeutic target.