p27kip1 controls cell morphology and motility by regulating microtubule-dependent lipid raft recycling

Barbara Belletti, Ilenia Pellizzari, Stefania Berton, Linda Fabris, Katarina Wolf, Francesca Lovat, Monica Schiappacassi, Sara D'Andrea, Milena S. Nicoloso, Sara Lovisa, Maura Sonego, Paola Defilippi, Andrea Vecchione, Alfonso Colombatti, Peter Friedl, Gustavo Baldassarre

Research output: Contribution to journalArticle

Abstract

p27kip1 (p27) is an inhibitor of cyclin/cyclin-dependent kinase complexes, whose nuclear loss indicates a poor prognosis in various solid tumors. When located in the cytoplasm, p27 binds Op18/stathmin (stathmin), a microtubule (MT)-destabilizing protein, and restrains its activity. This leads to MT stabilization, which negatively affects cell migration. Here, we demonstrate that this p27 function also influences morphology and motility of cells immersed in three-dimensional (3D)matrices. Cells lacking p27 display a decrease in MT stability, a rounded shape when immersed in 3D environments, and a mesenchymal-amoeboid conversion in their motility mode. Upon cell contact to extracellular matrix, the decreased MT stability observed in p27 null cells results in accelerated lipid raft trafficking and increased RhoA activity. Importantly, cell morphology, motility, MT network composition, and distribution of p27 null cells were rescued by the concomitant genetic ablation of Stathmin, implicating that the balanced expression of p27 and stathmin represents a crucial determinant for cytoskeletal organization and cellular behavior in 3D contexts.

Original languageEnglish
Pages (from-to)2229-2240
Number of pages12
JournalMolecular and Cellular Biology
Volume30
Issue number9
DOIs
Publication statusPublished - May 2010

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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    Belletti, B., Pellizzari, I., Berton, S., Fabris, L., Wolf, K., Lovat, F., Schiappacassi, M., D'Andrea, S., Nicoloso, M. S., Lovisa, S., Sonego, M., Defilippi, P., Vecchione, A., Colombatti, A., Friedl, P., & Baldassarre, G. (2010). p27kip1 controls cell morphology and motility by regulating microtubule-dependent lipid raft recycling. Molecular and Cellular Biology, 30(9), 2229-2240. https://doi.org/10.1128/MCB.00723-09