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

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Official URL:https://doi.org/10.1016/j.ccr.2009.12.043
PubMed:View item in PubMed
Creators Name:Reimann, M. and Lee, S. and Loddenkemper, C. and Doerr, J.R. and Tabor, V. and Aichele, P. and Stein, H. and Doerken, B. and Jenuwein, T. and Schmitt, C.A.
Journal Title:Cancer Cell
Journal Abbreviation:Cancer Cell
Volume:17
Number:3
Page Range:262-272
Date:16 March 2010
Keywords:Cellcycle, Animals, Mice
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.
ISSN:1535-6108
Publisher:Cell Press (U.S.A.)
Item Type:Article

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