JCB logo
Avanti Polar Lipids
  Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents
Published online March 24, 2008
doi:10.1083/jcb.200708137
The Journal of Cell Biology, Vol. 180, No. 6, 1277-1289
The Rockefeller University Press, 0021-9525 $30.00
© 2008 Shintani et al.
This Article
Right arrow Full Text
Right arrow PDF (Full Text)
Right arrow PPT slides of all figures
Right arrow Supplemental Material Index
Right arrow Alert me when this article is cited
Right arrow Citation Map
Services
Right arrow Email this article
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new content in the JCB
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via CrossRef
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Shintani, Y.
Right arrow Articles by Johnson, K. R.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Shintani, Y.
Right arrow Articles by Johnson, K. R.
Social Bookmarking
Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati  
What's this?

Article

 Collagen I–mediated up-regulation of N-cadherin requires cooperative signals from integrins and discoidin domain receptor 1

Yasushi Shintani1, Yuri Fukumoto2, Nina Chaika1, Robert Svoboda1, Margaret J. Wheelock1,2,3, and Keith R. Johnson1,2,3

1 Department of Oral Biology, 2 Eppley Institute for Research in Cancer and Allied Diseases, and 3 Eppley Cancer Center, University of Nebraska Medical Center, Omaha, NE 68198

Correspondence to Margaret J. Wheelock: mwheelock{at}unmc.edu

Tumor cells undergo epithelial-to-mesenchymal transition (EMT) to convert from a benign to a malignant phenotype. Our recent focus has been signaling pathways that promote EMT in response to collagen. We have shown that human pancreatic cancer cells respond to collagen by up-regulating N-cadherin, which promotes tumor growth, invasion, and metastasis. Initial characterization showed that knocking down c-Jun NH2-terminal kinase prevented N-cadherin up-regulation and limited tumor growth and invasion in a mouse model for pancreatic cancer. The current study was designed to understand the pathway from collagen to N-cadherin up-regulation. Initiation of the signal requires two collagen receptors, {alpha}2β1 integrin and discoidin domain receptor (DDR) 1. Each receptor propagates signals through separate pathways that converge to up-regulate N-cadherin. Focal adhesion kinase (FAK)–related protein tyrosine kinase (Pyk2) is downstream of DDR1, whereas FAK is downstream of {alpha}2β1 integrin. Both receptor complexes rely on the p130 Crk-associated substrate scaffold. Interestingly, Rap1, but not Rho family guanosine triphosphatases, is required for the response to collagen I.

Abbreviations used in this paper: CAS, Crk-associated substrate; CRIB, Cdc42-Rac interactive binding; DDR, discoidin domain receptor; EMT, epithelial-to-mesenchymal transition; MKK, MAPK kinase; MLK, mixed lineage kinase; pAb, polyclonal antibody; PAK, p21-activated kinase; PI3K, phosphatidylinositol 3-kinase; RIPA, radioimmunoprecipitation assay; SD, substrate domain; shRNA, short hairpin RNA; TNE, Tris/NP40/EDTA.


Add to CiteULike CiteULike   Add to Complore Complore   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Reddit Reddit   Add to Technorati Technorati    What's this?




  Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents