The Cleavage of Semaphorin 3C Induced by ADAMTS1 Promotes Cell Migration
The Cleavage of Semaphorin 3C Induced by ADAMTS1 Promotes Cell Migration
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DOI：
10.1074/jbc.m109.055129
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发表时间：
2010-01-22
影响因子：
4.8
通讯作者：
Arribas, Joaquin
中科院分区：
文献类型：
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作者：
Esselens, Cary;Malapeira, Jordi;Arribas, Joaquin
转移是一个连续的过程，允许细胞从原发肿瘤转移到其他地方生长。由于它们能够切割多种细胞外信号和粘附分子，金属蛋白酶长期以来被认为是转移程序的关键组成部分。然而，某些金属蛋白酶如ADAMTS 1的功能尚不清楚，似乎取决于细胞环境和/或肿瘤进展的阶段。为了表征ADAMTS 1的功能，我们进行了两种替代蛋白质组学方法，差异凝胶电泳和稳定同位素标记的氨基酸在细胞培养物中，以确定新的底物的金属蛋白酶。两种技术均显示ADAMTS 1的过表达导致脑信号蛋白3C从细胞外基质中释放。尽管脑信号蛋白是众所周知的轴突导向调节剂，但越来越多的证据表明它们也可能参与肿瘤的进展。在这里，我们表明ADAMTS 1诱导的信号蛋白3C的切割促进了乳腺癌细胞的迁移，这表明这些分子在肿瘤中的共表达可能有助于转移程序。
Metastasis is a sequential process that allows cells to move from the primary tumor and grow elsewhere. Because of their ability to cleave a variety of extracellular signaling and adhesion molecules, metalloproteases have been long considered key components of the metastatic program. However, the function of certain metalloproteases, such as ADAMTS1, is not clear and seems to depend on the cellular environment and/or the stage of tumor progression. To characterize the function of ADAMTS1, we performed two alternative proteomic approaches, difference gel electrophoresis and stable isotope labeling by amino acids in cell culture, to identify novel substrates of the metalloprotease. Both techniques showed that overexpression of ADAMTS1 leads to the release of semaphorin 3C from the extracellular matrix. Although semaphorins are well known regulators of axon guidance, accumulating evidence shows that they may also participate in tumor progression. Here, we show that the cleavage of semaphorin 3C induced by ADAMTS1 promotes the migration of breast cancer cells, indicating that the co-expression of these molecules in tumors may contribute to the metastatic program.