ArticleMolecular biology of the cell2001
Transforming growth factor beta enhances epithelial cell survival via Akt-dependent regulation of FKHRL1.
Article in Molecular biology of the cell, 2001. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 67 papers.
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Who cites it
67 citing papers in PubMed, 178 citations in OpenAlex.
- TGF-β1 maintains the developmental potential of embryonic submandibular gland epithelia separated with mesenchyme.Heliyon · 2024Article
- Oncolytic adenovirus encoding apolipoprotein A1 suppresses metastasis of triple-negative breast cancer in mice.Journal of experimental & clinical cancer research : CR · 2024Article
- TGF-β signaling in health, disease, and therapeutics.Signal transduction and targeted therapy · 2024Review
- From shape-shifting embryonic cells to oncology: The fascinating history of epithelial mesenchymal transition.Seminars in cancer biology · 2023Review
- PI3K block restores age-dependent neurovascular coupling defects associated with cerebral small vessel disease.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- TGF-β phospho antibody array identifies altered SMAD2, PI3K/AKT/SMAD, and RAC signaling contribute to the pathogenesis of myxomatous mitral valve disease.Frontiers in veterinary science · 2023Article
- Artemisinin and artemisinin derivatives as anti-fibrotic therapeutics.Acta pharmaceutica Sinica. B · 2021Review
- WAVE3 phosphorylation regulates the interplay between PI3K, TGF-β, and EGF signaling pathways in breast cancer.Oncogenesis · 2020Article
- Article
- Immunomodulatory Effects of TGF-β Family Signaling within Intestinal Epithelial Cells and Carcinomas.Gastrointestinal disorders (Basel, Switzerland) · 2019Article
- TGF-β downregulation-induced cancer cell death is finely regulated by the SAPK signaling cascade.Experimental & molecular medicine · 2018Article
- Differential role of PTEN in transforming growth factor β (TGF-β) effects on proliferation and migration in prostate cancer cells.The Prostate · 2018Article
- The secretome from bovine mammosphere-derived cells (MDC) promotes angiogenesis, epithelial cell migration, and contains factors associated with defense and immunity.Scientific reports · 2018Article
- Transforming growth factor-β in stem cells and tissue homeostasis.Bone research · 2018Article
- Single Nucleotide Polymorphism in SMAD7 and CHI3L1 and Colorectal Cancer Risk.Mediators of inflammation · 2018Review
- TGF-β upregulates the translation of USP15 via the PI3K/AKT pathway to promote p53 stability.Oncogene · 2017Article
- Calreticulin Is Required for TGF-β-Induced Epithelial-to-Mesenchymal Transition during Cardiogenesis in Mouse Embryonic Stem Cells.Stem cell reports · 2017Article
- TGF-β Family Signaling in the Control of Cell Proliferation and Survival.Cold Spring Harbor perspectives in biology · 2017Review
- Non-Smad Signaling Pathways of the TGF-β Family.Cold Spring Harbor perspectives in biology · 2017Review
- MED15 overexpression in prostate cancer arises during androgen deprivation therapy via PI3K/mTOR signaling.Oncotarget · 2017Article
7 more citing papers are in PubMed but not listed here.
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Authors and funding
5 authors at 3 institutions in 1 country.
Funding
Abstract
The Forkhead family of transcription factors participates in the induction of death-related genes. In NMuMG and 4T1 mammary epithelial cells, transforming growth factor beta (TGF beta) induced phosphorylation and cytoplasmic retention of the Forkhead factor FKHRL1, while reducing FHKRL1-dependent transcriptional activity. TGF beta-induced FKHRL1 phosphorylation and nuclear exclusion were inhibited by LY294002, an inhibitor of phosphatidylinositol-3 kinase. A triple mutant of FKHRL1, in which all three Akt phosphorylation sites have been mutated (TM-FKHRL1), did not translocate to the cytoplasm in response to TGF beta. In HaCaT keratinocytes, expression of dominant-negative Akt prevented TGF beta-induced 1) reduction of Forkhead-dependent transcription, 2) FKHRL1 phosphorylation, and 3) nuclear exclusion of FKRHL1. Forced expression of either wild-type (WT) or TM-FKHRL1, but not a FKHRL1 mutant with deletion of the transactivation domain, resulted in NMuMG mammary cell apoptosis. Evidence of nuclear fragmentation colocalized to cells with expression of WT- or TM-FKHRL1. The apoptotic effect of WT-FKHRL1 but not TM-FKHRL1 was prevented by exogenous TGF beta. Serum starvation-induced apoptosis was also inhibited by TGF beta in NMuMG and HaCaT cells. Finally, dominant-negative Akt abrogated the antiapoptotic effect of TGF beta. Taken together, these data suggest that TGF beta may play a role in epithelial cell survival via Akt-dependent regulation of FKHRL1.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.