Document Detail


The tumor suppressor functions of p27(kip1) include control of the mesenchymal/amoeboid transition.
MedLine Citation:
PMID:  19596789     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Stefania Berton; Barbara Belletti; Katarina Wolf; Vincenzo Canzonieri; Francesca Lovat; Andrea Vecchione; Alfonso Colombatti; Peter Friedl; Gustavo Baldassarre
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2009-07-13
Journal Detail:
Title:  Molecular and cellular biology     Volume:  29     ISSN:  1098-5549     ISO Abbreviation:  Mol. Cell. Biol.     Publication Date:  2009 Sep 
Date Detail:
Created Date:  2009-08-27     Completed Date:  2009-09-15     Revised Date:  2010-09-27    
Medline Journal Info:
Nlm Unique ID:  8109087     Medline TA:  Mol Cell Biol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  5031-45     Citation Subset:  IM    
Affiliation:
Division of Experimental Oncology 2, Centro di Riferimento Oncologico, Aviano, Italy.
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MeSH Terms
Descriptor/Qualifier:
Animals
Cell Line, Transformed
Cell Movement
Cell Proliferation
Cell Shape*
Cyclin-Dependent Kinase Inhibitor p27 / deficiency,  metabolism*
Fibroblasts / cytology,  metabolism
Mesoderm / cytology*,  metabolism
Mice
Microtubules / metabolism
Mutant Proteins / metabolism
Neoplasms / pathology
Oncogene Protein pp60(v-src) / metabolism
Phenotype
rhoA GTP-Binding Protein / metabolism
Chemical
Reg. No./Substance:
0/Mutant Proteins; 147604-94-2/Cyclin-Dependent Kinase Inhibitor p27; EC 2.7.10.2/Oncogene Protein pp60(v-src); EC 3.6.5.2/rhoA GTP-Binding Protein
Comments/Corrections

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