p27 super(Kip1)-stathmin interaction influences sarcoma cell migration and invasion

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 super(kip1) affects microtubule (MT) stability following cell adhesio...

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Bibliographic Details
Published in:Cancer cell 2005-01, Vol.7 (1), p.51-63
Main Authors: Baldassarre, G, Belletti, B, Nicoloso, MS, Schiappacassi, M, Vecchione, A, Spessotto, P, Morrione, A, Canzonieri, V, Colombatti, A
Format: Article
Language:English
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Summary: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 super(kip1) affects microtubule (MT) stability following cell adhesion on extracellular matrix (ECM) constituents. This p27 super(kip1) activity is due to its ability to bind and impair the function of the MT-destabilizing protein stathmin. Accordingly, upregulation of p27 super(kip1) or downregulation of stathmin expression results in the inhibition of mesenchymal cell motility. Moreover, high stathmin and low cytoplasmic p27 super(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 super(kip1) in different subcellular compartments.
ISSN:1535-6108
DOI:10.1016/j.ccr.2004.11.025