The integrin cytoplasmic-tail motif EKQKVDLSTDC is sufficient to promote tumor cell invasion mediated by matrix metalloproteinase (MMP)-2 or MMP-9
The integrin cytoplasmic-tail motif EKQKVDLSTDC is sufficient to promote tumor cell invasion mediated by matrix metalloproteinase (MMP)-2 or MMP-9
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DOI：
10.1074/jbc.m401736200
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发表时间：
2004-06-18
影响因子：
4.8
通讯作者：
Marshall, JF
中科院分区：
文献类型：
--
作者：
Morgan, MR;Thomas, GJ;Marshall, JF
整合素通过多种活性的组合促进细胞侵袭，包括粘附至细胞外基质配体，这导致产生导致细胞行为改变的细胞内信号。到目前为止，还没有数据确定整合素亚基的胞质尾区的特定区域特异性地负责促进肿瘤细胞的侵袭活性。在这份报告中，我们表明，氨基酸序列EKQKVDLSTDC，这是整合素β 6亚基的C-末端残基，促进α v β 6依赖的侵袭基质金属蛋白酶（MMP）-9依赖的方式。当在β 3整联蛋白亚基的胞质末端表达时，这种相同的肽序列能够以MMP-2依赖性方式增强α v β 3介导的肿瘤细胞的侵袭和酶活性。我们的研究结果表明，这11个氨基酸，当在β亚基的C末端表达时，负责调节侵袭促进降解酶的活性，而参与这种细胞行为的特定MMP依赖于β整联蛋白亚基的其余部分的上下文。
Integrins promote cellular invasion through a combination of activities, including adhesion to an extracellular matrix ligand, which result in the generation of intracellular signals that lead to changes in cell behavior. Until now, there have been no data that identify a particular region of the cytoplasmic tail of integrin subunits as being responsible specifically for promoting the invasive activity of tumor cells. In this report, we show that amino acids with the sequence EKQKVDLSTDC, which are the C-terminal residues of the integrin beta6 subunit, promote alphavbeta6-dependent invasion in a matrix metalloproteinase (MMP)-9-dependent fashion. This same peptide sequence, when expressed at the cytoplasmic end of the beta3 integrin subunit, was able to enhance alphavbeta3-mediated invasive and enzymatic activity of tumor cells in an MMP-2-dependent fashion. Our results show that these 11 amino acids, when expressed at the C terminus of the beta subunit, are responsible for regulating the activity of invasion-promoting degradative enzymes, whereas the specific MMP involved in this cellular behavior is dependent on the context of the remainder of the beta integrin subunit.