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  Tumor Stroma-Derived TGF-β Limits Myc-Driven Lymphoma-genesis via Suv39h1-Dependent Senescence

Reimann, M., Lee, S., Loddenkemper, C., Dörr, J. R., Tabor, V., Aichele, P., et al. (2010). Tumor Stroma-Derived TGF-β Limits Myc-Driven Lymphoma-genesis via Suv39h1-Dependent Senescence. Cancer Cell, 17, 262-272.

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Item Permalink: http://hdl.handle.net/11858/00-001M-0000-002B-8E99-2 Version Permalink: http://hdl.handle.net/11858/00-001M-0000-002B-8E9A-F
Genre: Journal Article

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 Creators:
Reimann, Maurice, Author
Lee, Soyoung, Author
Loddenkemper, Christoph, Author
Dörr, Jan R., Author
Tabor, Vedrana, Author
Aichele, Peter, Author
Stein, Harald, Author
Dörken, Bernd, Author
Jenuwein, Thomas1, Author              
Schmitt, Clemens A., Author
Affiliations:
1Department of Epigenetics, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society, ou_2243644              

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 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 Eμ-myc transgenic mouse lymphoma model, we show here in vivo that apoptotic lymphoma cells activate macrophages to secrete transforming growth factor β (TGF-β) as a critical non-cell-autonomous inducer of cellular senescence. Accordingly, neutralization of TGF-β 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.

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Language(s): eng - English
 Dates: 2010-03-16
 Publication Status: Published in print
 Pages: -
 Publishing info: -
 Table of Contents: -
 Rev. Type: Peer
 Identifiers: eDoc: 534594
 Degree: -

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Title: Cancer Cell
Source Genre: Journal
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Pages: - Volume / Issue: 17 Sequence Number: - Start / End Page: 262 - 272 Identifier: -