![[Feedback]](/icons/banner/feedbackACT.gif){kind=icon}
![[For Subscribers]](/icons/banner/subscriberACT.gif){kind=icon}
![[Archive]](/icons/banner/archiveACT.gif){kind=icon}
![[Search]](/icons/banner/searchACT.gif){kind=icon}
![[Contents]](/icons/banner/tocACT.gif){kind=icon}
|
|
|
|
|
||
Vol. 14, Issue 5, 1964-1977, May 2003
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
* Istituto di Neurobiologia e Medicina Molecolare, CNR, 00137 Rome, Italy;
EMBL, Mouse Biology Programme, 00016 Monterotondo, Italy;
Istituto Superiore di Sanità, 00100 Rome, Italy; and
¶ Istituto di Biologia Cellulare, CNR, 00016 Monterotondo, Italy
Submitted August 7, 2002;
Revised November 28, 2002;
Accepted January 16, 2003
Monitoring Editor: Richard Assoian
Cadherin-mediated cell–cell adhesion is dynamically modulated during epithelial–mesenchymal transition triggered by activation of receptor tyrosine kinases (RTK) in epithelial cells. Several cadherin-binding proteins have been identified that control cell–cell adhesion. However, the mechanisms by which intercellular adhesion and cell motility are coregulated are still unknown. Here, we delineate a hitherto uncharted cooperation between RTKs, RhoA GTPase, and p120 catenin in instructing a motile behavior to epithelial cells. We found that expression of an N-terminus–deleted p120 catenin in a variety of epithelial cell types, including primary keratinocytes, effectively competes for endogenous p120 at cadherin binding sites and abrogates EGF-stimulated cell motility as well as HGF-induced cell scattering. The deleted mutant also inhibits the PI3K-dependent RhoA activation ensuing receptor activation. Conversely, we also show that the ectopic expression of full-length p120 in epithelial cells promotes cytoskeletal changes, stimulates cell motility, and activates RhoA. Both motogenic response to p120 and RhoA activation require coactivation of signaling downstream of RTKs as they are suppressed by ablation of the Ras/PI3K pathway. These studies demonstrate that p120 catenin is a necessary target of RTKs in regulating cell motility and help define a novel pathway leading to RhoA activation, which may contribute to the early steps of metastatic invasion.
Both authors contributed equally to this work.
# Corresponding authors. E-mail address: alema{at}ibc.rm.cnr.it; ams{at}im.rm.cnr.it.
This article has been cited by other articles:
|
|
 |
|
  M. Yanagisawa, D. Huveldt, P. Kreinest, C. M. Lohse, J. C. Cheville, A. S. Parker, J. A. Copland, and P. Z. Anastasiadis A p120 Catenin Isoform Switch Affects Rho Activity, Induces Tumor Cell Invasion, and Predicts Metastatic Disease J. Biol. Chem., June 27, 2008; 283(26): 18344 - 18354. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Mimeault and S. K. Batra Interplay of distinct growth factors during epithelial mesenchymal transition of cancer progenitor cells and molecular targeting as novel cancer therapies Ann. Onc., October 1, 2007; 18(10): 1605 - 1619. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Ichii and M. Takeichi p120-catenin regulates microtubule dynamics and cell migration in a cadherin-independent manner Genes Cells, July 1, 2007; 12(7): 827 - 839. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Boguslavsky, I. Grosheva, E. Landau, M. Shtutman, M. Cohen, K. Arnold, E. Feinstein, B. Geiger, and A. Bershadsky p120 catenin regulates lamellipodial dynamics and cell adhesion in cooperation with cortactin PNAS, June 26, 2007; 104(26): 10882 - 10887. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Castellani, E. Salvati, S. Alema, and G. Falcone Fine Regulation of RhoA and Rock Is Required for Skeletal Muscle Differentiation J. Biol. Chem., June 2, 2006; 281(22): 15249 - 15257. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Sato, N. Fujita, A. Yamada, T. Ooshio, R. Okamoto, K. Irie, and Y. Takai Regulation of the Assembly and Adhesion Activity of E-cadherin by Nectin and Afadin for the Formation of Adherens Junctions in Madin-Darby Canine Kidney Cells J. Biol. Chem., February 24, 2006; 281(8): 5288 - 5299. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. A. Gimelbrant, A. W. Ensminger, P. Qi, J. Zucker, and A. Chess Monoallelic Expression and Asynchronous Replication of p120 Catenin in Mouse and Human Cells J. Biol. Chem., January 14, 2005; 280(2): 1354 - 1359. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. I. Chernyavsky, J. Arredondo, L. M. Marubio, and S. A. Grando Differential regulation of keratinocyte chemokinesis and chemotaxis through distinct nicotinic receptor subtypes J. Cell Sci., November 1, 2004; 117(23): 5665 - 5679. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Z. M. Jaffer and J. Chernoff The Cross-Rho'ds of Cell-Cell Adhesion J. Biol. Chem., August 20, 2004; 279(34): 35123 - 35126. [Full Text] [PDF]
|
|
|
|
 |
|
 T. Shibata, A. Kokubu, S. Sekine, Y. Kanai, and S. Hirohashi Cytoplasmic p120ctn Regulates the Invasive Phenotypes of E-Cadherin-Deficient Breast Cancer Am. J. Pathol., June 1, 2004; 164(6): 2269 - 2278. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. J. Mariner, M. A. Davis, and A. B. Reynolds EGFR signaling to p120-catenin through phosphorylation at Y228 J. Cell Sci., March 15, 2004; 117(8): 1339 - 1350. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Suriano, M. J. Oliveira, D. Huntsman, A. R. Mateus, P. Ferreira, F. Casares, C. Oliveira, F. Carneiro, J. C. Machado, M. Mareel, et al. E-cadherin germline missense mutations and cell phenotype: evidence for the independence of cell invasion on the motile capabilities of the cells Hum. Mol. Genet., November 15, 2003; 12(22): 3007 - 3016. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Wong and P. A. Coulombe Loss of keratin 6 (K6) proteins reveals a function for intermediate filaments during wound repair J. Cell Biol., October 27, 2003; 163(2): 327 - 337. [Abstract] [Full Text] [PDF]
|
|
