| The tumor suppressor functions of p27(kip1) include control of the mesenchymal/amoeboid transition. | |
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MedLine Citation:
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PMID: 19596789 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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Stefania Berton; Barbara Belletti; Katarina Wolf; Vincenzo Canzonieri; Francesca Lovat; Andrea Vecchione; Alfonso Colombatti; Peter Friedl; Gustavo Baldassarre |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2009-07-13 |
Journal Detail:
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Title: Molecular and cellular biology Volume: 29 ISSN: 1098-5549 ISO Abbreviation: Mol. Cell. Biol. Publication Date: 2009 Sep |
Date Detail:
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Created Date: 2009-08-27 Completed Date: 2009-09-15 Revised Date: 2010-09-27 |
Medline Journal Info:
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Nlm Unique ID: 8109087 Medline TA: Mol Cell Biol Country: United States |
Other Details:
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Languages: eng Pagination: 5031-45 Citation Subset: IM |
Affiliation:
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Division of Experimental Oncology 2, Centro di Riferimento Oncologico, Aviano, Italy. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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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:
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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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