The DOI matches its Crossref record; 48 of the 48 references it cites were found in a registry or an index.
Phosphatidylinositol 3-Kinase Function Is Required for Transforming Growth Factor β-mediated Epithelial to Mesenchymal Transition and Cell Migration
Open accessAbstract
We have studied the role of phosphatidylinositol 3-OH kinase (PI3K)-Akt signaling in transforming growth factor beta (TGFbeta)-mediated epithelial to mesenchymal transition (EMT). In NMuMG mammary epithelial cells, exogenous TGFbeta1 induced phosphorylation of Akt at Ser-473 and Akt in vitro kinase activity against GSK-3beta within 30 min. These responses were temporally correlated with delocalization of E-cadherin, ZO-1, and integrin beta(1) from cell junctions and the acquisition of spindle cell morphology. LY294002, an inhibitor of the p110 catalytic subunit of PI3K, and a dominant-negative mutant of Akt blocked the delocalization of ZO-1 induced by TGFbeta1, whereas transfection of constitutively active p110 induced loss of ZO-1 from tight junctions. In addition, LY294002 blocked TGFbeta-mediated C-terminal phosphorylation of Smad2. Consistent with these data, TGFbeta-induced p3TP-Lux and p(CAGA)(12)-Lux reporter activities were inhibited by LY294002 and transiently expressed dominant-negative p85 and Akt mutants in NMuMG and 4T1 cells. Dominant-negative RhoA inhibited TGFbeta-induced phosphorylation of Akt at Ser-473, whereas constitutively active RhoA increased the basal phosphorylation of Akt, suggesting that RhoA in involved in TGFbeta-induced EMT. Finally, LY294002 and neutralizing TGFbeta1 antibodies inhibited ligand-independent constitutively active Akt as well as basal and TGFbeta-stimulated migration in 4T1 and EMT6 breast tumor cells. Taken together, these data suggest that PI3K-Akt signaling is required for TGFbeta-induced transcriptional responses, EMT, and cell migration.
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Cites
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Cited by
Molecular mechanisms of epithelial–mesenchymal transition
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TGF-β-induced epithelial to mesenchymal transition
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Regulation of the Polarity Protein Par6 by TGFß Receptors Controls Epithelial Cell Plasticity
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Metadata
- Authors
- Bakin, A. V., Tomlinson, A. K., Bhowmick, N. A., Moses, H. L., & Arteaga, C. L.
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2000-11
- Volume
- 275
- Issue
- 47
- Pages
- 36803-36810
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W1983628734
- Cited by
- 992
- References
- 48
- FWCI
- 9.01
- Type
- journal article
- Language
- en
- Open access
- hybrid
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- Bakin, A. V., Tomlinson, A. K., Bhowmick, N. A., Moses, H. L., & Arteaga, C. L. (2000). Phosphatidylinositol 3-Kinase Function Is Required for Transforming Growth Factor β-mediated Epithelial to Mesenchymal Transition and Cell Migration. Journal of Biological Chemistry. https://doi.org/10.1074/jbc.m005912200
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