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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. and Lee, S. and Loddenkemper, C. and Dörr, J.R. and Tabor, V. and Aichele, P. and Stein, H. and Doerken, B. and 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 |
| ISSN: | 1535-6108 |
| Publisher: | Cell Press / Elsevier |
| Volume: | 17 |
| Number: | 3 |
| 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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