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首页> 外文期刊>Biological chemistry >Metastasis-associated C4.4A, a GPI-anchored protein cleaved by ADAM10 and ADAM17
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Metastasis-associated C4.4A, a GPI-anchored protein cleaved by ADAM10 and ADAM17

机译：转移相关的C4.4A，由ADAM10和ADAM17裂解的GPI锚定蛋白

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Metalloproteases play a complex role in tumor progression. While the activity of some ADAM, ADAMTS and matrix metalloproteases (MMPs) seems to be protumorigenic, the activity of others seems to prevent tumor progression. The identification of the array of substrates of a given metalloprotease (degradome) seems an adequate approach to predict the effect of the inhibition of a metalloprotease in tumors. Here, we present the proteomic identification of a novel substrate for ADAM10 and -17. We used SILAC (Stable Isotope Labeling by Amino acids in Cell culture), a proteomic technique based on the differential metabolic labeling of cells in different conditions. This was applied to MCF7 cells derived from an invasive mammary tumor, and the same cells expressing shRNAs that knock down ADAM10 or -17. Following this approach, we have identified C4.4A as a substrate to both metalloproteases. Since C4.4A is likely involved in tumor invasion, these results indicate that the cleavage of C4.4A by ADAM10 and ADAM17 contributes to tumor progression
机译：金属蛋白酶在肿瘤进展中起着复杂的作用。虽然某些ADAM，ADAMTS和基质金属蛋白酶（MMP）的活性似乎是致瘤的，但其他活性似乎阻止了肿瘤的进展。鉴定给定金属蛋白酶（降解组）的底物阵列似乎是预测肿瘤中金属蛋白酶抑制作用的适当方法。在这里，我们介绍了ADAM10和-17的新型底物的蛋白质组学鉴定。我们使用了SILAC（细胞培养中氨基酸的稳定同位素标记）技术，这是一种蛋白质组学技术，基于不同条件下细胞的差异代谢标记。将其应用于衍生自浸润性乳腺肿瘤的MCF7细胞，以及表达敲低ADAM10或-17的shRNA的相同细胞。按照这种方法，我们已经确定C4.4A是两种金属蛋白酶的底物。由于C4.4A可能参与了肿瘤侵袭，因此这些结果表明，ADAM10和ADAM17对C4.4A的切割有助于肿瘤的进展

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