Regulation of matrix metalloproteinase-9 and inhibition of tumor invasion by the membrane-anchored glycoprotein RECK
Regulation of matrix metalloproteinase-9 and inhibition of tumor invasion by the membrane-anchored glycoprotein RECK
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DOI：
10.1073/pnas.95.22.13221
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发表时间：
1998-10-27
影响因子：
11.1
通讯作者：
Noda, M
中科院分区：
文献类型：
--
作者：
Takahashi, C;Sheng, ZQ;Noda, M
筛选人成纤维细胞 cDNA 表达文库中的 cDNA 克隆，当转染到 v-Ki-ras 转化的 NIH 3T3 细胞中时，会产生扁平集落。其中一种基因 RECK 编码约 110 kDa 的膜锚定糖蛋白，具有多个表皮生长因子样重复序列和丝氨酸蛋白酶抑制剂样结构域。虽然 RECK mRNA 在各种人体组织和未转化细胞中表达，但在肿瘤衍生细胞系和致癌转化细胞中检测不到。恶性细胞中RECK表达的恢复导致侵袭活性受到抑制，同时基质金属蛋白酶9（MMP-9）（一种参与肿瘤侵袭和转移的关键酶）的分泌减少。此外，发现纯化的 RECK 蛋白与 MMP-9 结合并抑制其蛋白水解活性。因此，RECK可能将致癌信号与肿瘤侵袭和转移联系起来。
A human fibroblast cDNA expression library was screened for cDNA clones giving rise to flat colonies when transfected into v-Ki-ras-transformed NIH 3T3 cells. One such gene, RECK, encodes a membrane-anchored glycoprotein of about 110 kDa with multiple epidermal growth factor-like repeats and serine-protease inhibitor-like domains, While RECK mRNA is expressed in various human tissues and untransformed cells, it is undetectable in tumor-derived cell lines and oncogenically transformed cells. Restored expression of RECK in malignant cells resulted in suppression of invasive activity with concomitant decrease in the secretion of matrix metalloproteinase-9 (MMP-9), a key enzyme involved in tumor invasion and metastasis. Moreover, purified RECK protein was found to bind to, and inhibit the proteolytic activity of, MMP-9. Thus, RECK may link oncogenic signals to tumor invasion and metastasis.