p27^Kip1-stathmin interaction influences sarcoma cell migration and invasion

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• 作者：Gustavo Baldassarre ; Barbara Belletti ; Milena S. Nicoloso ; Monica Schiappacassi ; Andrea Vecchione ; Paola Spessotto ; Andrea Morrione ; Vincenzo Canzonieri ; Alfonso Colombatti
• 刊名：Cancer Cell
• 出版年：2005
• 出版时间：January 2005
• 年：2005
• 卷：7
• 期：1
• 页码：51-63
• 全文大小：833 K

文摘

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.