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首页> 外文期刊>EBioMedicine >Novel role of APP cleavage by ADAM10 for breast cancer metastasis
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Novel role of APP cleavage by ADAM10 for breast cancer metastasis

机译：ADAM10切割APP对乳腺癌转移的新作用

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Cleavage of the amyloid precursor protein (APP) at the membrane-proximal extracellular position, termed the alpha secretase site, prevents the generation of amyloidogenic Aβ peptide (Fig. 1). Since the aggregation of Aβ peptides has been associated with the development of Alzheimer's disease the responsible α-secretase became an important subject of research. Almost 20?years ago this protease was identified as ADAM10 which stands for a disintegrin and a metalloproteinase [1]. Since then, researchers identified an increasing number of other ADAM10 substrates most prominently including Notch, EGF-like growth factors, some adhesion molecules, and ephrins and their receptors. Besides its function in development which largely depends on the cleavage of Notch, ADAM10 was found to play crucial roles in physiologic and pathophysiologic processes. Accumulating evidence suggests an important involvement of ADAM10 in migration of various cell types including leukocytes, various tissue cells, and cancer cells [2]. It seems that the underlying mechanisms can be very diverse owing to ADAM10's numerous substrates including ephrins, growth factors, adhesion molecules, transmembrane chemokines or respective receptors.
机译：淀粉样前体蛋白（APP）在膜近端胞外位置的切割（称为α分泌酶位点）阻止了产生淀粉样蛋白的Aβ肽的产生（图1）。由于Aβ肽的聚集与阿尔茨海默氏病的发展有关，负责任的α分泌酶成为重要的研究课题。大约20年前，该蛋白酶被鉴定为ADAM10，代表全整合素和金属蛋白酶[1]。从那时起，研究人员发现了数量越来越多的其他ADAM10底物，其中最突出的包括Notch，EGF样生长因子，一些粘附分子以及ephrins及其受体。除了其在发育中的功能在很大程度上取决于Notch的裂解外，还发现ADAM10在生理和病理生理过程中起着至关重要的作用。越来越多的证据表明，ADAM10参与了包括白细胞，各种组织细胞和癌细胞在内的各种细胞类型的迁移[2]。似乎由于ADAM10的众多底物（包括麻黄素，生长因子，粘附分子，跨膜趋化因子或各自的受体），其潜在机制可能非常多样化。

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