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

50 Citations (Scopus)

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

Fingerprint

Stathmin
Recycling
Microtubules
Cell Movement
Lipids
Null Lymphocytes
Microtubule Proteins
Cyclins
Cyclin-Dependent Kinases
Extracellular Matrix
Cytoplasm
Neoplasms

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Cite this

p27kip1 controls cell morphology and motility by regulating microtubule-dependent lipid raft recycling. / Belletti, Barbara; Pellizzari, Ilenia; Berton, Stefania; Fabris, Linda; Wolf, Katarina; Lovat, Francesca; Schiappacassi, Monica; D'Andrea, Sara; Nicoloso, Milena S.; Lovisa, Sara; Sonego, Maura; Defilippi, Paola; Vecchione, Andrea; Colombatti, Alfonso; Friedl, Peter; Baldassarre, Gustavo.

In: Molecular and Cellular Biology, Vol. 30, No. 9, 05.2010, p. 2229-2240.

Research output: Contribution to journalArticle

Belletti, B, Pellizzari, I, Berton, S, Fabris, L, Wolf, K, Lovat, F, Schiappacassi, M, D'Andrea, S, Nicoloso, MS, 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, vol. 30, no. 9, pp. 2229-2240. https://doi.org/10.1128/MCB.00723-09
Belletti, Barbara ; Pellizzari, Ilenia ; Berton, Stefania ; Fabris, Linda ; Wolf, Katarina ; Lovat, Francesca ; Schiappacassi, Monica ; D'Andrea, Sara ; Nicoloso, Milena S. ; Lovisa, Sara ; Sonego, Maura ; Defilippi, Paola ; Vecchione, Andrea ; Colombatti, Alfonso ; Friedl, Peter ; Baldassarre, Gustavo. / p27kip1 controls cell morphology and motility by regulating microtubule-dependent lipid raft recycling. In: Molecular and Cellular Biology. 2010 ; Vol. 30, No. 9. pp. 2229-2240.
@article{7176da2754bb4504a859635923ebdedc,
title = "p27kip1 controls cell morphology and motility by regulating microtubule-dependent lipid raft recycling",
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.",
author = "Barbara Belletti and Ilenia Pellizzari and Stefania Berton and Linda Fabris and Katarina Wolf and Francesca Lovat and Monica Schiappacassi and Sara D'Andrea and Nicoloso, {Milena S.} and Sara Lovisa and Maura Sonego and Paola Defilippi and Andrea Vecchione and Alfonso Colombatti and Peter Friedl and Gustavo Baldassarre",
year = "2010",
month = "5",
doi = "10.1128/MCB.00723-09",
language = "English",
volume = "30",
pages = "2229--2240",
journal = "Molecular and Cellular Biology",
issn = "0270-7306",
publisher = "American Society for Microbiology",
number = "9",

}

TY - JOUR

T1 - p27kip1 controls cell morphology and motility by regulating microtubule-dependent lipid raft recycling

AU - Belletti, Barbara

AU - Pellizzari, Ilenia

AU - Berton, Stefania

AU - Fabris, Linda

AU - Wolf, Katarina

AU - Lovat, Francesca

AU - Schiappacassi, Monica

AU - D'Andrea, Sara

AU - Nicoloso, Milena S.

AU - Lovisa, Sara

AU - Sonego, Maura

AU - Defilippi, Paola

AU - Vecchione, Andrea

AU - Colombatti, Alfonso

AU - Friedl, Peter

AU - Baldassarre, Gustavo

PY - 2010/5

Y1 - 2010/5

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=77950676582&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=77950676582&partnerID=8YFLogxK

U2 - 10.1128/MCB.00723-09

DO - 10.1128/MCB.00723-09

M3 - Article

C2 - 20194624

AN - SCOPUS:77950676582

VL - 30

SP - 2229

EP - 2240

JO - Molecular and Cellular Biology

JF - Molecular and Cellular Biology

SN - 0270-7306

IS - 9

ER -