P27kip1 Controls Cell Morphology and Motility by Regulating Microtubule-dependent Lipid Raft Recycling

Overview

Journal Mol Cell Biol

Specialty Cell Biology

Date 2010 Mar 3

PMID 20194624

Citations 38

Authors

Barbara Belletti

Ilenia Pellizzari

Stefania Berton

Linda Fabris

Katarina Wolf

Francesca Lovat

Monica Schiappacassi

Sara DAndrea

Milena S Nicoloso

Sara Lovisa

Maura Sonego

Paola Defilippi

Andrea Vecchione

Alfonso Colombatti

Peter Friedl

Gustavo Baldassarre

Affiliations

Soon will be listed here.

Abstract

p27(kip1) (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.

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