MiR-21/Smad 7 signaling determines TGF-β1-induced CAF formation
Qiong Li,Daoxiang Zhang,Yongbin Wang,Pan Sun,Xiaodan Hou,James M. Larner,Wujun Xiong,Jun Mi,Jun Mi +8 more
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TLDR
It is demonstrated that miR-21 and Smad7 are critical regulators of TGF-β1 signaling during the induction of CAF formation.Abstract:
How TGF-β1-mediated signaling pathways are finely tuned to orchestrate the generation of carcinoma-associated fibroblasts (CAFs) is poorly understood Here, we demonstrate that miR-21 and the signaling of its target Smad 7 determine TGF-β1-induced CAF formation In primary cultured fibroblasts, mature miR-21 increases after TGF-β1 treatment, whereas the Smad 7 protein level decreases MiR-21 binds to the 3′ UTR of Smad7 mRNA and inhibits its translation, rather than causing its degradation Most importantly, Smad 7 is bound to Smad 2 and 3, which are thought to competitively bind to TGFBR1 and prevents their activation upon TGF-β1 stimulation The depletion of miR-21 or the overexpression of Smad 7 blocks TGF-β1-induced CAF formation, whereas the overexpression of miR-21 or the depletion of Smad 7 promotes CAF formation, even without TGF-β1 stimulation Collectively, these findings clearly demonstrate that miR-21 and Smad7 are critical regulators of TGF-β1 signaling during the induction of CAF formationread more
Citations
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MicroRNA therapeutics: towards a new era for the management of cancer and other diseases
TL;DR: Recent advances in the understanding of miRNAs in cancer and in other diseases are described and the challenge of identifying the most efficacious therapeutic candidates is discussed and a perspective on achieving safe and targeted delivery of miRNA therapeutics is provided.
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Carcinoma-associated fibroblasts: orchestrating the composition of malignancy
Philippe Gascard,Thea D. Tlsty +1 more
TL;DR: Novel insights into the contributions of CAFs to disease progression, emergent events leading to the generation ofCAFs, identification of CAF-specific biomarkers predictive of disease outcome, and recent therapeutic approaches aimed at blunting or reverting detrimental protumorigenic phenotypes associated with CAFs are focused on.
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miRNA Deregulation in Cancer Cells and the Tumor Microenvironment
TL;DR: Insight is provided into the regulatory mechanisms involved in the deregulation of miRNAs in cancer cells and the tumor microenvironment and therapeutic intervention strategies to overcome this deregulation are discussed.
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Exosomes released by chronic lymphocytic leukemia cells induce the transition of stromal cells into cancer-associated fibroblasts
Jérôme Paggetti,Franziska Haderk,Martina Seiffert,Bassam Janji,Ute Distler,Wim Ammerlaan,Yeoun Jin Kim,Julien Adam,Peter Lichter,Eric Solary,Guy Berchem,Etienne Moussay +11 more
TL;DR: It is demonstrated that CLL-derived exosomes actively promote disease progression by modulating several functions of surrounding stromal cells that acquire features of cancer-associated fibroblasts, contributing to a tumor-supportive microenvironment.
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Regulation of TGF-β Family Signaling by Inhibitory Smads.
Keiji Miyazawa,Kohei Miyazono +1 more
TL;DR: The vertebrate I-Smads, their roles as inhibitors of Smad activation and regulators of receptor stability, as scaffolds for non-Smad signaling, and their possible roles in the nucleus are discussed.
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