![[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, 2002
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Submitted on October 1, 2001
Revised on December 20, 2001
Accepted on January 18, 2002
1 Molecular Oncology Group, McGill University Hospital Center, Department of Biochemistry, McGill University, Montreal, Quebec, Canada
2 Molecular Oncology Group, McGill University Hospital Center, Department of Medicine, McGill University, Montreal, Quebec, Canada (present address: Ste-Justine Hospital, Department of Pediatrics, University of Montreal, Montreal, Quebec, Canada)
3 Molecular Oncology Group, McGill University Hospital Center, Department of Medicine, McGill University, Montreal, Quebec, Canada
4 Molecular Oncology Group, McGill University Hospital Center, Departments of Biochemistry, Medicine and Oncology, McGill University, Montreal, Quebec, Canada
* Corresponding author. E-mail address: morag{at}lan1.molonc.mcgill.ca.
Activation of the Met receptor tyrosine kinase through its ligand, hepatocyte growth factor (HGF), promotes an epithelial-mesenchymal transition and cell dispersal. However, little is known about the HGF-dependent signals that regulate these events. HGF stimulation of epithelial cell colonies leads to the enhanced recruitment of the CrkII and CrkL adapter proteins to Met-dependent signaling complexes. We provide evidence that signals involving CrkII and CrkL are required for the breakdown of adherens junctions, the spreading of epithelial colonies and the formation of lamellipodia in response to HGF. The overexpression of a CrkI SH3 domain mutant blocks these HGF-dependent events. In addition, the overexpression of CrkII or CrkL promotes lamellipodia formation, loss of adherens junctions, cell spreading and dispersal of colonies of breast cancer epithelial cells in the absence of HGF. Stable lines of epithelial cells overexpressing CrkII show enhanced activation of Rac1 and Rap1. The Crk-dependent breakdown of adherens junctions and cell spreading is inhibited by the expression of a dominant negative mutant of Rac1 but not Rap1. These findings provide evidence that Crk adapter proteins play a critical role in the breakdown of adherens junctions and the spreading of sheets of epithelial cells.
This article has been cited by other articles:
|
|
 |
|
  F. Chianale, S. Cutrupi, E. Rainero, G. Baldanzi, P. E. Porporato, S. Traini, N. Filigheddu, V. F. Gnocchi, M. M. Santoro, O. Parolini, et al. Diacylglycerol Kinase-{alpha} Mediates Hepatocyte Growth Factor-induced Epithelial Cell Scatter by Regulating Rac Activation and Membrane Ruffling Mol. Biol. Cell, December 1, 2007; 18(12): 4859 - 4871. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. K. Noren and E. B. Pasquale Paradoxes of the EphB4 Receptor in Cancer Cancer Res., May 1, 2007; 67(9): 3994 - 3997. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Leibowitz-Amit, G. Tsarfaty, Y. Abargil, G. M. Yerushalmi, J. Horev, and I. Tsarfaty Mimp, a Mitochondrial Carrier Homologue, Inhibits Met-HGF/SF-Induced Scattering and Tumorigenicity by Altering Met-HGF/SF Signaling Pathways. Cancer Res., September 1, 2006; 66(17): 8687 - 8697. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Mood, C. Saucier, Y.-S. Bong, H.-S. Lee, M. Park, and I. O. Daar Gab1 Is Required for Cell Cycle Transition, Cell Proliferation, and Transformation Induced by an Oncogenic Met Receptor Mol. Biol. Cell, September 1, 2006; 17(9): 3717 - 3728. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Watanabe, M. Tsuda, Y. Makino, S. Ichihara, H. Sawa, A. Minami, N. Mochizuki, K. Nagashima, and S. Tanaka Adaptor Molecule Crk Is Required for Sustained Phosphorylation of Grb2-Associated Binder 1 and Hepatocyte Growth Factor-Induced Cell Motility of Human Synovial Sarcoma Cell Lines Mol. Cancer Res., July 1, 2006; 4(7): 499 - 510. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Suzuki, H. Mimuro, T. Suzuki, M. Park, T. Yamamoto, and C. Sasakawa Interaction of CagA with Crk plays an important role in Helicobacter pylori-induced loss of gastric epithelial cell adhesion J. Exp. Med., November 7, 2005; 202(9): 1235 - 1247. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. V. Abella, P. Peschard, M. A. Naujokas, T. Lin, C. Saucier, S. Urbe, and M. Park Met/Hepatocyte Growth Factor Receptor Ubiquitination Suppresses Transformation and Is Required for Hrs Phosphorylation Mol. Cell. Biol., November 1, 2005; 25(21): 9632 - 9645. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Q. Deng, J. Sun, and J. T. Barbieri Uncoupling Crk Signal Transduction by Pseudomonas Exoenzyme T J. Biol. Chem., October 28, 2005; 280(43): 35953 - 35960. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. P. Rodrigues, K. E. Fathers, G. Chan, D. Zuo, F. Halwani, S. Meterissian, and M. Park CrkI and CrkII Function as Key Signaling Integrators for Migration and Invasion of Cancer Cells Mol. Cancer Res., April 1, 2005; 3(4): 183 - 194. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Prindull and D. Zipori Environmental guidance of normal and tumor cell plasticity: epithelial mesenchymal transitions as a paradigm Blood, April 15, 2004; 103(8): 2892 - 2899. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M.-H. Wang, D. Wang, and Y.-Q. Chen Oncogenic and invasive potentials of human macrophage-stimulating protein receptor, the RON receptor tyrosine kinase Carcinogenesis, August 1, 2003; 24(8): 1291 - 1300. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Lamorte, S. Rodrigues, V. Sangwan, C. E. Turner, and M. Park Crk Associates with a Multimolecular Paxillin/GIT2/{beta}-PIX Complex and Promotes Rac-dependent Relocalization of Paxillin to Focal Contacts Mol. Biol. Cell, July 1, 2003; 14(7): 2818 - 2831. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Takino, M. Nakada, H. Miyamori, J. Yamashita, K. M. Yamada, and H. Sato CrkI Adapter Protein Modulates Cell Migration and Invasion in Glioblastoma Cancer Res., May 1, 2003; 63(9): 2335 - 2337. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. R. Maroun, M. A. Naujokas, and M. Park Membrane Targeting of Grb2-associated Binder-1 (Gab1) Scaffolding Protein through Src Myristoylation Sequence Substitutes for Gab1 Pleckstrin Homology Domain and Switches an Epidermal Growth Factor Response to an Invasive Morphogenic Program Mol. Biol. Cell, April 1, 2003; 14(4): 1691 - 1708. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Lamorte, S. Rodrigues, M. Naujokas, and M. Park Crk Synergizes with Epidermal Growth Factor for Epithelial Invasion and Morphogenesis and Is Required for the Met Morphogenic Program J. Biol. Chem., September 27, 2002; 277(40): 37904 - 37911. [Abstract] [Full Text] [PDF]
|
|
