Document Detail


TGF-β-induced activation of mTOR complex 2 drives epithelial-mesenchymal transition and cell invasion.
MedLine Citation:
PMID:  22399812     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
In cancer progression, carcinoma cells gain invasive behavior through a loss of epithelial characteristics and acquisition of mesenchymal properties, a process that can lead to epithelial-mesenchymal transition (EMT). TGF-β is a potent inducer of EMT, and increased TGF-β signaling in cancer cells is thought to drive cancer-associated EMT. Here, we examine the physiological requirement for mTOR complex 2 (mTORC2) in cells undergoing EMT. TGF-β rapidly induces mTORC2 kinase activity in cells undergoing EMT, and controls epithelial cell progression through EMT. By regulating EMT-associated cytoskeletal changes and gene expression, mTORC2 is required for cell migration and invasion. Furthermore, inactivation of mTORC2 prevents cancer cell dissemination in vivo. Our results suggest that the mTORC2 pathway is an essential downstream branch of TGF-β signaling, and represents a responsive target to inhibit EMT and prevent cancer cell invasion and metastasis.
Authors:
Samy Lamouille; Erin Connolly; James W Smyth; Rosemary J Akhurst; Rik Derynck
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2012-03-07
Journal Detail:
Title:  Journal of cell science     Volume:  125     ISSN:  1477-9137     ISO Abbreviation:  J. Cell. Sci.     Publication Date:  2012 Mar 
Date Detail:
Created Date:  2012-04-11     Completed Date:  2012-09-25     Revised Date:  2013-06-26    
Medline Journal Info:
Nlm Unique ID:  0052457     Medline TA:  J Cell Sci     Country:  England    
Other Details:
Languages:  eng     Pagination:  1259-73     Citation Subset:  IM    
Affiliation:
Department of Cell and Tissue Biology, University of California at San Francisco, San Francisco, CA 94143-0512, USA.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:
Animals
Carcinoma, Squamous Cell / metabolism,  pathology
Carrier Proteins / genetics,  metabolism*
Cell Line, Tumor
Cell Movement
Disease Progression
Epithelial Cells / metabolism
Epithelial-Mesenchymal Transition*
Matrix Metalloproteinase 9 / biosynthesis
Mice
Neoplasm Invasiveness
Neoplasms / metabolism,  pathology
Phosphorylation
Proto-Oncogene Proteins c-akt / metabolism
RNA Interference
RNA, Messenger / biosynthesis
RNA, Small Interfering
Signal Transduction / physiology
TOR Serine-Threonine Kinases / metabolism*
Transcription Factors / genetics
Transforming Growth Factor beta / metabolism*
rhoA GTP-Binding Protein / metabolism
Grant Support
ID/Acronym/Agency:
P01-HL60231/HL/NHLBI NIH HHS; R01 CA136690/CA/NCI NIH HHS; R01-CA116019/CA/NCI NIH HHS; R01-CA136690/CA/NCI NIH HHS; R01-GM60514/GM/NIGMS NIH HHS; R01-HL078564/HL/NHLBI NIH HHS; T32 CA108462/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
0/Carrier Proteins; 0/RNA, Messenger; 0/RNA, Small Interfering; 0/Transcription Factors; 0/Transforming Growth Factor beta; 0/rictor protein, mouse; 0/snail family transcription factors; 0/stress-activated protein kinase-interacting protein, mouse; EC 2.7.1.1/TOR Serine-Threonine Kinases; EC 2.7.1.1/mTOR protein, mouse; EC 2.7.11.1/Proto-Oncogene Proteins c-akt; EC 3.4.24.35/Matrix Metalloproteinase 9; EC 3.6.5.2/rhoA GTP-Binding Protein
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


Previous Document:  Role of shear-stress-induced VEGF expression in endothelial cell survival.
Next Document:  Urinary vanin-1 as a novel biomarker for early detection of drug-induced acute kidney injury.