| 1. |
- Bergström, Rosita, et al.
(författare)
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Transforming growth factor β promotes complexes between Smad proteins and the CCCTC-binding factor on the H19 imprinting control region chromatin
- 2010
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Ingår i: Journal of Biological Chemistry. - USA : The American Society for Biochemistry and Molecular Biology, Inc.. - 0021-9258 .- 1083-351X. ; 285:26, s. 19727-19737
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Tidskriftsartikel (refereegranskat)abstract
- Whether signal transduction pathways regulate epigenetic states in response to environmental cues remains poorly understood. We demonstrate here that Smad3, signaling downstream of transforming growth factor beta, interacts with the zinc finger domain of CCCTC-binding factor (CTCF), a nuclear protein known to act as "the master weaver of the genome." This interaction occurs via the Mad homology 1 domain of Smad3. Although Smad2 and Smad4 fail to interact, an alternatively spliced form of Smad2 lacking exon 3 interacts with CTCF. CTCF does not perturb well established transforming growth factor beta gene responses. However, Smads and CTCF co-localize to the H19 imprinting control region (ICR), which emerges as an insulator in cis and regulator of transcription and replication in trans via direct CTCF binding to the ICR. Smad recruitment to the ICR requires intact CTCF binding to this locus. Smad2/3 binding to the ICR requires Smad4, which potentially provides stability to the complex. Because the CTCF-Smad complex is not essential for the chromatin insulator function of the H19 ICR, we propose that it can play a role in chromatin cross-talk organized by the H19 ICR.
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| 2. |
- Caja, Laia, et al.
(författare)
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Snail regulates BMP and TGF beta pathways to control the differentiation status of glioma-initiating cells
- 2018
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Ingår i: Oncogene. - : Springer Science and Business Media LLC. - 0950-9232 .- 1476-5594. ; 37:19, s. 2515-2531
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Tidskriftsartikel (refereegranskat)abstract
- Glioblastoma multiforme is a brain malignancy characterized by high heterogeneity, invasiveness, and resistance to current therapies, attributes related to the occurrence of glioma stem cells (GSCs). Transforming growth factor beta (TGF beta) promotes self-renewal and bone morphogenetic protein (BMP) induces differentiation of GSCs. BMP7 induces the transcription factor Snail to promote astrocytic differentiation in GSCs and suppress tumor growth in vivo. We demonstrate that Snail represses stemness in GSCs. Snail interacts with SMAD signaling mediators, generates a positive feedback loop of BMP signaling and transcriptionally represses the TGFB1 gene, decreasing TGF beta 1 signaling activity. Exogenous TGF beta 1 counteracts Snail function in vitro, and in vivo promotes proliferation and re-expression of Nestin, confirming the importance of TGFB1 gene repression by Snail. In conclusion, novel insight highlights mechanisms whereby Snail differentially regulates the activity of the opposing BMP and TGF beta pathways, thus promoting an astrocytic fate switch and repressing stemness in GSCs.
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| 5. |
- Savary, Katia, et al.
(författare)
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Role of TGF-β signaling in EMT, cancer progression and metastasis
- 2011
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Ingår i: Drug Discovery Today. - : Elsevier. - 1740-6757. ; 8:2-3, s. 121-126
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Tidskriftsartikel (refereegranskat)abstract
- Transforming growth factor b (TGFb) signaling isimplicated in cancer progression since its discovery.Although TGFb plays tumor suppressor roles, thesame pathway also provides pro-tumorigenic fates.The pro-tumorigenic action of TGFb involves processeslike epithelial–mesenchymal transition (EMT),tumor microenvironment remodeling, and eventuallymetastatic dissemination to new sites of tumor growth.Here, we give an updated overview of TGFb roles intumor progression and emphasize current evaluationsof TGFb blockade in preventing EMT and metastasis.
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