JCB logo
  Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents
Published online
doi:10.1083/jcb.200611146
The Journal of Cell Biology, Vol. 178, No. 3, 437-451
The Rockefeller University Press, 0021-9525 $30.00
© Lamouille et al.
This Article
Right arrow Full Text
Right arrow Full Text (PDF, 3118K)
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 HighWire
Right arrow Citing Articles via CrossRef
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Lamouille, S.
Right arrow Articles by Derynck, R.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Lamouille, S.
Right arrow Articles by Derynck, R.
Right arrowPubmed/NCBI databases
*Compound via MeSH
*Substance via MeSH
Related Collections
Right arrowRelated Article
Social Bookmarking
Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Facebook   Add to Reddit   Add to Technorati   Add to Twitter  
What's this?

Article

Cell size and invasion in TGF-ß–induced epithelial to mesenchymal transition is regulated by activation of the mTOR pathway



Samy Lamouille and Rik Derynck

Department of Cell and Tissue Biology, Program in Cell Biology, University of California, San Francisco, San Francisco, CA 94143

Correspondence to Rik Derynck: rik.derynck{at}ucsf.edu

Epithelial to mesenchymal transition (EMT) occurs during development and cancer progression to metastasis and results in enhanced cell motility and invasion. Transforming growth factor-ß (TGF-ß) induces EMT through Smads, leading to transcriptional regulation, and through non-Smad pathways. We observe that TGF-ß induces increased cell size and protein content during EMT. This translational regulation results from activation by TGF-ß of mammalian target of rapamycin (mTOR) through phosphatidylinositol 3-kinase and Akt, leading to the phosphorylation of S6 kinase 1 and eukaryotic initiation factor 4E–binding protein 1, which are direct regulators of translation initiation. Rapamycin, a specific inhibitor of mTOR complex 1, inhibits the TGF-ß–induced translation pathway and increase in cell size without affecting the EMT phenotype. Additionally, rapamycin decreases the migratory and invasive behavior of cells that accompany TGF-ß–induced EMT. The TGF-ß–induced translation pathway through mTOR complements the transcription pathway through Smads. Activation of mTOR by TGF-ß, which leads to increased cell size and invasion, adds to the role of TGF-ß–induced EMT in cancer progression and may represent a therapeutic opportunity for rapamycin analogues in cancer.

Abbreviations used in this paper: 4E-BP1, eukaryotic initiation factor 4E–binding protein 1; EMT, epithelial to mesenchymal transition; F-actin, filamentous actin; IGF-1, insulin-like growth factor-1; mTOR, mammalian target of rapamycin; mTORC, mTOR complex; PI3K, phosphatidylinositol 3-kinase; S6K1, S6 kinase 1; TßR, TGF-ß receptor; TSC, tuberous sclerosis complex; ZO-1, zonula occludens-1.


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 Facebook Facebook   Add to Reddit Reddit   Add to Technorati Technorati   Add to Twitter Twitter    What's this?

Related Article

Small cancer cells don't stray
Mitch Leslie
J. Cell Biol. 2007 178: 339. [Full Text] [PDF]



This article has been cited by other articles:



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