Cell size and invasion in TGF-β–induced epithelial to mesenchymal transition is regulated by activation of the mTOR pathway
S Lamouille, R Derynck - The Journal of cell biology, 2007 - rupress.org
S Lamouille, R Derynck
The Journal of cell biology, 2007•rupress.orgEpithelial to mesenchymal transition (EMT) occurs during development and cancer
progression to metastasis and results in enhanced cell motility and invasion. Transforming
growth factor-β (TGF-β) induces EMT through Smads, leading to transcriptional regulation,
and through non-Smad pathways. We observe that TGF-β induces increased cell size and
protein content during EMT. This translational regulation results from activation by TGF-β of
mammalian target of rapamycin (mTOR) through phosphatidylinositol 3-kinase and Akt …
progression to metastasis and results in enhanced cell motility and invasion. Transforming
growth factor-β (TGF-β) induces EMT through Smads, leading to transcriptional regulation,
and through non-Smad pathways. We observe that TGF-β induces increased cell size and
protein content during EMT. This translational regulation results from activation by TGF-β of
mammalian target of rapamycin (mTOR) through phosphatidylinositol 3-kinase and Akt …
Epithelial to mesenchymal transition (EMT) occurs during development and cancer progression to metastasis and results in enhanced cell motility and invasion. Transforming growth factor-β (TGF-β) induces EMT through Smads, leading to transcriptional regulation, and through non-Smad pathways. We observe that TGF-β induces increased cell size and protein content during EMT. This translational regulation results from activation by TGF-β 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-β–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-β–induced EMT. The TGF-β–induced translation pathway through mTOR complements the transcription pathway through Smads. Activation of mTOR by TGF-β, which leads to increased cell size and invasion, adds to the role of TGF-β–induced EMT in cancer progression and may represent a therapeutic opportunity for rapamycin analogues in cancer.
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