Document Detail


Emergence of the phosphoinositide 3-kinase-Akt-mammalian target of rapamycin axis in transforming growth factor-β-induced epithelial-mesenchymal transition.
MedLine Citation:
PMID:  21041997     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
During development and in pathological contexts such as fibrosis and cancer progression, epithelial cells can initiate a complex transcriptional reprogramming, accompanied by dramatic morphological changes, in a process named 'epithelial-mesenchymal transition' (EMT). In this transition, epithelial cells lose their epithelial characteristics to acquire mesenchymal properties and increased motile and invasive behavior. Transforming growth factor-β (TGF-β) has emerged as a major inducer of EMT through activation of downstream signaling pathways, including Smad and non-Smad signaling pathways. Among the non-Smad pathways, increasing evidence is emerging that the phosphoinositide 3-kinase-Akt-mammalian target of rapamycin axis plays a major role in TGF-β-induced EMT, notably through the regulation of translation and cell invasion. Pharmacological inhibitors of the phosphoinositide 3-kinase-Akt-mammalian target of rapamycin pathway may therefore represent an opportunity to selectively target essential aspects of TGF-β-induced EMT and provide an approach to prevent cancer cell dissemination toward metastasis, without the need to fully inactivate TGF-β signaling.
Authors:
Samy Lamouille; Rik Derynck
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Review     Date:  2010-11-02
Journal Detail:
Title:  Cells, tissues, organs     Volume:  193     ISSN:  1422-6421     ISO Abbreviation:  Cells Tissues Organs (Print)     Publication Date:  2011  
Date Detail:
Created Date:  2010-12-16     Completed Date:  2011-03-31     Revised Date:  2013-07-03    
Medline Journal Info:
Nlm Unique ID:  100883360     Medline TA:  Cells Tissues Organs     Country:  Switzerland    
Other Details:
Languages:  eng     Pagination:  8-22     Citation Subset:  IM    
Copyright Information:
Copyright © 2010 S. Karger AG, Basel.
Affiliation:
Department of Cell and Tissue Biology, Program in Cell Biology, University of California, San Francisco, CA 94143-0512, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Epithelial-Mesenchymal Transition / drug effects*
Humans
Phosphatidylinositol 3-Kinase / metabolism*
Proto-Oncogene Proteins c-akt / metabolism*
TOR Serine-Threonine Kinases / metabolism*
Transforming Growth Factor beta / pharmacology*
Grant Support
ID/Acronym/Agency:
P01-HL60231/HL/NHLBI NIH HHS; R01-CA136690/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
0/Transforming Growth Factor beta; EC 2.7.1.1/TOR Serine-Threonine Kinases; EC 2.7.1.137/Phosphatidylinositol 3-Kinase; EC 2.7.11.1/Proto-Oncogene Proteins c-akt
Comments/Corrections

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