TGF-β-induced activation of mTOR complex 2 drives epithelial–mesenchymal transition and cell invasion
0301 basic medicine
0303 health sciences
Epithelial-Mesenchymal Transition
Epithelial Cells
3. Good health
Mice
03 medical and health sciences
Rapamycin-Insensitive Companion of mTOR Protein
Matrix Metalloproteinase 9
Cell Movement
Cell Line, Tumor
Neoplasms
Carcinoma, Squamous Cell
Disease Progression
Animals
Neoplasm Invasiveness
RNA Interference
RNA, Messenger
Snail Family Transcription Factors
Phosphorylation
RNA, Small Interfering
Carrier Proteins
Proto-Oncogene Proteins c-akt
Signal Transduction
DOI:
10.1242/jcs.095299
Publication Date:
2012-03-08T03:39:14Z
AUTHORS (5)
ABSTRACT
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.
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