Human Molecular Genetics Advance Access published online on September 18, 2003
Human Molecular Genetics, doi:10.1093/hmg/ddg316
© 2003 by Oxford University Press
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
1 Instituto de Patologia e Imunologia Molecular da Universidade do Porto (IPATIMUP), 4200-465 Porto, Portugal
* To whom correspondence should be addressed. E-mail: rseruca{at}ipatimup.pt.
In Hereditary Diffuse Gastric Cancer syndrome E-cadherin germline mutations of the missense type harbour significant functional consequences. In this study, we have characterised the effect of T340A, A617T, A634V and V832M E-cadherin germline missense mutations on cell morphology, motility and proliferation. Wild-type E-cadherin and A617T expressing cells have an epithelial-like morphology, with polarised cells migrating unidirectionally. T340A and A634V expressing cells, fibroblast-like, have a high motile phenotype. We show that this phenotype is dependent on an increased level of active RhoA. V832M expressing cells grow in piled-up structure of round cells, as an effect of the disturbance of the binding between
Article
E-cadherin germline missense mutations and cell phenotype: evidence for the independence of cell invasion on the motile capabilities of the cells
2 Laboratory of Experimental Cancerology, Ghent University Hospital, B-9000 Ghent, Belgium
3 Department of Pathology and Laboratory Medicine, University of British Columbia Vancouver, Canada
4 Instituto de Biologia Molecular e Celular (IBMC), Universidade do Porto, 4150-180, Porto, Portugal
5 Instituto de Patologia e Imunologia Molecular da Universidade do Porto (IPATIMUP), 4200-465 Porto, Portugal; Faculdade de Medicina, 4200-465 Porto, Portugal; Serviço de Anatomia Patológica, Hospital S. João, 4200-465 Porto, Portugal
6 Instituto de Patologia e Imunologia Molecular da Universidade do Porto (IPATIMUP), 4200-465 Porto, Portugal; Faculdade de Medicina, 4200-465 Porto, Portugal
Abstract 
-catenin and 
-catenin. The destabilisation of the adhesion complex is shown to hamper the motile capabilities of these cells. We did not observe any effect of the E-cadherin mutations on cell proliferation. We show the existence of a genotype-phenotype correlation between different E-cadherin mutations and cell behaviour. However, we demonstrate that the ability of cells expressing the different E-cadherin mutations to invade is independent on their motile capabilities, providing evidences that motility is neither necessary nor sufficient for cells to invade. Our data gives new insights into the understanding of the mechanisms linking invasion and E-cadherin mutations in diffuse gastric cancer.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  J. Deplazes, M. Fuchs, S. Rauser, H. Genth, E. Lengyel, R. Busch, and B. Luber Rac1 and Rho contribute to the migratory and invasive phenotype associated with somatic E-cadherin mutation Hum. Mol. Genet., October 1, 2009; 18(19): 3632 - 3644. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Bajpai, J. Correia, Y. Feng, J. Figueiredo, S. X. Sun, G. D. Longmore, G. Suriano, and D. Wirtz {alpha}-Catenin mediates initial E-cadherin-dependent cell-cell recognition and subsequent bond strengthening PNAS, November 25, 2008; 105(47): 18331 - 18336. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F Carneiro, C Oliveira, G Suriano, and R Seruca Molecular pathology of familial gastric cancer, with an emphasis on hereditary diffuse gastric cancer J. Clin. Pathol., January 1, 2008; 61(1): 25 - 30. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. R. Mateus, R. Seruca, J. C. Machado, G. Keller, M. J. Oliveira, G. Suriano, and B. Luber EGFR regulates RhoA-GTP dependent cell motility in E-cadherin mutant cells Hum. Mol. Genet., July 1, 2007; 16(13): 1639 - 1647. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Kaurah, A. MacMillan, N. Boyd, J. Senz, A. De Luca, N. Chun, G. Suriano, S. Zaor, L. Van Manen, C. Gilpin, et al. Founder and Recurrent CDH1 Mutations in Families With Hereditary Diffuse Gastric Cancer JAMA, June 6, 2007; 297(21): 2360 - 2372. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. S. Pereira, A. Teixeira, S. Pinho, P. Ferreira, J. Fernandes, C. Oliveira, R. Seruca, G. Suriano, and F. Casares E-cadherin missense mutations, associated with hereditary diffuse gastric cancer (HDGC) syndrome, display distinct invasive behaviors and genetic interactions with the Wnt and Notch pathways in Drosophila epithelia Hum. Mol. Genet., May 15, 2006; 15(10): 1704 - 1712. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Oliveira, R. Seruca, and F. Carneiro Genetics, Pathology, and Clinics of Familial Gastric Cancer International Journal of Surgical Pathology, January 1, 2006; 14(1): 21 - 33. [Abstract] [PDF]
|
|