The tumor suppressor functions of p27kip1 include control of the mesenchymal/amoeboid transition

Stefania Berton, Barbara Belletti, Katarina Wolf, Vincenzo Canzonieri, Francesca Lovat, Andrea Vecchione, Alfonso Colombatti, Peter Friedl, Gustavo Baldassarre

Research output: Contribution to journalArticle

Abstract

In many human cancers, p27 downregulation correlates with a worse prognosis, suggesting that p27 levels could represent an important determinant in cell transformation and cancer development. Using a mouse model system based on v-src-induced transformation, we show here that p27 absence is always linked to a more aggressive phenotype. When cultured in three-dimensional contexts, v-src-transformed p27-null fibroblasts undergo a morphological switch from an elongated to a rounded cell shape, accompanied by amoeboid-like morphology and motility. Importantly, the acquisition of the amoeboid motility is associated with a greater ability to move and colonize distant sites in vivo. The reintroduction of different p27 mutants in v-src-transformed p27-null cells demonstrates that the control of cell proliferation and motility represents two distinct functions of p27, both necessary for it to fully act as a tumor suppressor. Thus, we highlight here a new p27 function in driving cell plasticity that is associated with its C-terminal portion and does not depend on the control of cyclin-dependent kinase activity.

Original languageEnglish
Pages (from-to)5031-5045
Number of pages15
JournalMolecular and Cellular Biology
Volume29
Issue number18
DOIs
Publication statusPublished - Sep 2009

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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