This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Supplemental material
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Google Scholar
Right arrow Articles by Berton, S.
Right arrow Articles by Baldassarre, G.
PubMed
Right arrow PubMed Citation
Right arrow Articles by Berton, S.
Right arrow Articles by Baldassarre, G.

 Previous Article  |  Next Article 

Molecular and Cellular Biology, September 2009, p. 5031-5045, Vol. 29, No. 18
0270-7306/09/$08.00+0     doi:10.1128/MCB.00144-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

The Tumor Suppressor Functions of p27kip1 Include Control of the Mesenchymal/Amoeboid Transition{triangledown} ,{dagger}

Stefania Berton,1 Barbara Belletti,1 Katarina Wolf,2 Vincenzo Canzonieri,3 Francesca Lovat,1 Andrea Vecchione,4 Alfonso Colombatti,1,5 Peter Friedl,2 and Gustavo Baldassarre1*

Division of Experimental Oncology 2, Centro di Riferimento Oncologico, Istituto Nazionale Tumori, IRCCS Aviano 33081, Italy,1 Microscopical Imaging of the Cell, Department of Cell Biology, NCMLS, Radboud University Nijmegen Medical Centre, 6500 HB Nijmegen, The Netherlands,2 Division of Pathology, Centro di Riferimento Oncologico, Istituto Nazionale Tumori, IRCCS Aviano 33081, Italy,3 Division of Pathology, II Faculty of Medicine, University La Sapienza, Ospedale Sant'Andrea, Rome, Italy,4 Dipartimento di Scienze e Tecnologie Biomediche, and MATI Center of Excellence, University of Udine, 33100 Udine, Italy5

Received 1 February 2009/ Returned for modification 9 March 2009/ Accepted 2 July 2009

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.

* Corresponding author. Mailing address: Division of Experimental Oncology 2, Centro di Riferimento Oncologico, Via Franco Gallini, 2, 33081 Aviano, Italy. Phone: 39 0434 659 233. Fax: 39 0434 659 428. E-mail: gbaldassarre{at}cro.it

{triangledown} Published ahead of print on 13 July 2009.

{dagger} Supplemental material for this article may be found at http://mcb.asm.org/.

Molecular and Cellular Biology, September 2009, p. 5031-5045, Vol. 29, No. 18
0270-7306/09/$08.00+0     doi:10.1128/MCB.00144-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»