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Tumor stroma-derived TGF-beta limits Myc-driven lymphomagenesis via Suv39h1-dependent senescence

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Item Type:Article
Title:Tumor stroma-derived TGF-beta limits Myc-driven lymphomagenesis via Suv39h1-dependent senescence
Creators Name:Reimann, M., Lee, S., Loddenkemper, C., Dörr, J.R., Tabor, V., Aichele, P., Stein, H., Doerken, B., Jenuwein, T. and Schmitt, C.A.
Abstract:Activated RAS/BRAF oncogenes induce cellular senescence as a tumor-suppressive barrier in early cancer development, at least in part, via an oncogene-evoked DNA damage response (DDR). In contrast, Myc activation-although producing a DDR as well-is known to primarily elicit an apoptotic countermeasure. Using the Emu-myc transgenic mouse lymphoma model, we show here in vivo that apoptotic lymphoma cells activate macrophages to secrete transforming growth factor beta (TGF-beta) as a critical non-cell-autonomous inducer of cellular senescence. Accordingly, neutralization of TGF-beta action, like genetic inactivation of the senescence-related histone methyltransferase Suv39h1, significantly accelerates Myc-driven tumor development via cancellation of cellular senescence. These findings, recapitulated in human aggressive B cell lymphomas, demonstrate that tumor-prompted stroma-derived signals may limit tumorigenesis by feedback senescence induction.
Keywords:Cellcycle, Animals, Mice
Source:Cancer Cell
Publisher:Cell Press / Elsevier
Page Range:262-272
Date:16 March 2010
Official Publication:https://doi.org/10.1016/j.ccr.2009.12.043
PubMed:View item in PubMed

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