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Transforming Growth Factor–B Signaling in Stem Cells and Cancer Summary

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Jennifer Huang

on 1 October 2012

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Transcript of Transforming Growth Factor–B Signaling in Stem Cells and Cancer Summary

is a cytokine, a signaling molecule, that binds to receptors to initiate different pathways in cells TGF-B TGF-B and related factors like BMP, activin, and nodal bind to type I and type II receptors and activate different Smads that lead to different cell activity Smad Pathway Smad 2 and 3 form a complex with Smad 4 and ultimately leads to inhibition of proliferation http://www.nature.com/nrm/journal/v8/n11/images/nrm2262-f1.jpg Smad 1/5/8 form a complex with Smad 4 to act as a co-activator for pro-cell cycle molecules like cyclins Smad 1/5/8 Smad 2/3 Smad 1/3/8 competes with Smad 2/3 to bind to Smad 4 Various factors determine the effect of TFG-B family proteins on the cell Differentiation Stage Environment Timing Ligand Dosage/Gradient TGF-B leads to mesoderm differentiation Smad 6/7 inhibits other Smads and leads to apoptosis Activin induces mesoderm and endoderm differentiation BMP signals result in the differentiation of ectoderm and mesoderm Nodal maintains pluripotency in ES cells, especially that of neural cells When TGF-B signaling components are inactivated, gastrointestinal tumors are almost sure to develop In hematopoietic stem cells, BMPs promote differentiation and proliferation, which is opposite of TGF-B In mesenchymal cells, TGF-B expression is activated by injury In mesenchymal cells, BMPs activate differentiation of osteoblasts (bone cells) BMPs at high dosages cause neural cells to undergo apoptosis In gastrointestinal cells, BMPs supress the Wnt pathway, decreasing proliferation and limiting renewal of stem cells In a cancerous environment of neural cells, TGF-B promotes tumor formation instead of preventing it For example, TGF-B inhibits the proliferation of early
multi-potent hematopoietic stem cells but not that of later progenitors. TGF-B inhibits differentiation of uncommitted neural, hematopoietic, mesenchymal, and gastrointestinal ES cells, but once a precursor lineage is accelerates differentiation determined, TGF-B BMPs inhibit the proliferation of neural progenitors at embryonic day 13 but facilitate differentiation on day 16 Overall, TBF-B family proteins have a significant impact on the path a cell takes, playing various roles in the self-renewal and differentiation processes.
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