p27Kip1-stathmin interaction influences sarcoma cell migration and invasion
p27Kip1-stathmin interaction influences sarcoma cell migration and invasion
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DOI：
10.1016/j.ccr.2004.11.025
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发表时间：
2005-01-01
期刊：
影响因子：
50.3
通讯作者：
Colombatti, A
中科院分区：
文献类型：
--
作者：
Baldassarre, G;Belletti, B;Colombatti, A
新的证据表明，细胞周期蛋白依赖性激酶抑制剂（CKIs）可以调节细胞周期进程以外的细胞功能，如分化和迁移。在这里，我们报告，细胞质表达的p27（kip1）影响微管（MT）的稳定性细胞粘附在细胞外基质（ECM）成分。这种p27（kip1）活性是由于其结合MT去稳定蛋白stathmin并损害其功能的能力。因此，上调p27（kip1）或下调stathmin的表达导致间充质细胞运动的抑制。此外，高stathmin和低细胞质p27（kip1）表达与体内人肉瘤的转移表型相关。这项研究提供了一个功能之间的联系，肿瘤细胞的增殖和侵袭的基础上不同的活动p27（kip1）在不同的亚细胞区室。
Emerging evidences suggest that cyclin-dependent kinase inhibitors (CKIs) can regulate cellular functions other than cell cycle progression, such as differentiation and migration. Here, we report that cytoplasmic expression of p27(kip1) affects microtubule (MT) stability following cell adhesion on extracellular matrix (ECM) constituents. This p27(kip1) activity is due to its ability to bind and impair the function of the MT-destabilizing protein stathmin. Accordingly, upregulation of p27(kip1) or downregulation of stathmin expression results in the inhibition of mesenchymal cell motility. Moreover, high stathmin and low cytoplasmic p27(kip1) expression correlate with the metastatic phenotype of human sarcomas in vivo. This study provides a functional link between proliferation and invasion of tumor cells based on diverse activities of p27(kip1) in different subcellular compartments.