![[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}
|
|
|
|
|
||
A more recent version of this article appeared on May 1, 2003
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Submitted on August 7, 2002
Revised on November 28, 2002
Accepted on January 16, 2003
1 Istituto di Neurobiologia e Medicina Molecolare, C.N.R., 00137 Rome, Italy
2 EMBL, Mouse Biology Programme, 00016 Monterotondo, Italy
3 Istituto Superiore di Sanità, 00100 Rome, Italy
4 Istituto di Biologia Cellulare, C.N.R., 00016 Monterotondo, Italy
* Corresponding author. E-mail address: ams{at}in.rm.cnr.it.
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 co-regulated are still unknown. Here, we delineate a hitherto uncharted cooperation between RTKs, RhoA GTPase and p120 catenin in instructing a motile behaviour 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 co-activation of signalling 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.
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]
|
|
