LIM kinase1 modulates function of membrane type matrix metalloproteinase 1: implication in invasion of prostate cancer cells.
LIM kinase1 modulates function of membrane type matrix metalloproteinase 1: implication in invasion of prostate cancer cells.
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DOI：
10.1186/1476-4598-10-6
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发表时间：
2011-01-10
期刊：
影响因子：
37.3
通讯作者：
Chakrabarti R
中科院分区：
文献类型：
--
作者：
Tapia T;Ottman R;Chakrabarti R
LIM激酶1（LIMK 1）是肌动蛋白和微管细胞骨架调节蛋白，其在许多癌组织和细胞中过表达，并且还促进前列腺癌和乳腺癌细胞的侵袭和转移。膜型基质金属蛋白酶1（MT 1-MMP）是细胞外基质（ECM）通过细胞周围蛋白水解的关键调节剂，因此在肿瘤细胞的侵袭和转移中起着至关重要的作用。MT 1-MMP及其底物pro-MMP-2和pro-MMP-9通常在包括前列腺癌在内的多种癌症中过表达，并且表达水平与前列腺癌细胞中的恶性程度相关。本研究的目的是确定LIMK 1和MT 1-MMP之间的任何功能关系及其在细胞侵袭中的意义。我们的研究结果表明，用MT 1-MMP、MMP-2和MMP-9的异羟肟酸抑制剂伊洛马司他治疗抑制了LIMK 1诱导的良性前列腺上皮细胞的侵袭。LIMK 1的过度表达导致MMP-2的胶原溶解活性增加，以及MMP-2和MMP-9的分泌增加。过表达LIMK 1的细胞也表现出MT 1-MMP表达增加，转录激活及其定位于质膜。LIMK 1与MT 1-MMP物理结合并与其共定位于高尔基体囊泡。我们还注意到MT 1-MMP和LIMK 1在前列腺肿瘤组织中的表达增加。我们的研究结果提供了新的信息MT 1-MMP功能的LIMK 1的调节，并首次显示，在LIMK 1诱导的细胞侵袭的MMPs的参与。
LIM kinase 1 (LIMK1) is an actin and microtubule cytoskeleton modulatory protein that is overexpressed in a number of cancerous tissues and cells and also promotes invasion and metastasis of prostate and breast cancer cells. Membrane type matrix metalloproteinase 1 (MT1-MMP) is a critical modulator of extracellular matrix (ECM) turnover through pericellular proteolysis and thus plays crucial roles in neoplastic cell invasion and metastasis. MT1-MMP and its substrates pro-MMP-2 and pro-MMP-9 are often overexpressed in a variety of cancers including prostate cancer and the expression levels correlate with the grade of malignancy in prostate cancer cells. The purpose of this study is to determine any functional relation between LIMK1 and MT1-MMP and its implication in cell invasion. Our results showed that treatment with the hydroxamate inhibitor of MT1-MMP, MMP-2 and MMP-9 ilomastat inhibited LIMK1-induced invasion of benign prostate epithelial cells. Over expression of LIMK1 resulted in increased collagenolytic activity of MMP-2, and secretion of pro-MMP2 and pro-MMP-9. Cells over expressing LIMK1 also exhibited increased expression of MT1-MMP, transcriptional activation and its localization to the plasma membrane. LIMK1 physically associates with MT1-MMP and is colocalized with it to the Golgi vesicles. We also noted increased expression of both MT1-MMP and LIMK1 in prostate tumor tissues. Our results provide new information on regulation of MT1-MMP function by LIMK1 and showed for the first time, involvement of MMPs in LIMK1 induced cell invasion.
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影响因子：
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作者：
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通讯作者：
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发表时间：
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影响因子：
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