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The Myc/macrophage tango: Oncogene-induced senescence, Myc style

Item Type:Review
Title:The Myc/macrophage tango: Oncogene-induced senescence, Myc style
Creators Name:Lee, S. and Schmitt, C.A. and Reimann, M.
Abstract:Ras/Raf-prototypic oncogenes induce cellular senescence, a terminal cell-cycle arrest, as a default cellular safeguard program, while oncogenic Myc is known to rather promote apoptosis as the prime failsafe mechanism. We review and discuss here evidence for Myc-induced senescence - which is detectable to a limited degree as a cell-autonomous, direct response to Myc action, but occurs predominantly in a non-cell-autonomous fashion via crosstalk of the oncogene-driven cell population with non-neoplastic bystanders, namely cells of the host immune system, prompting them to release pro-senescent cytokines that strike back onto adjacent proliferating tumor cells. In particular, we discuss how Myc-evoked apoptosis serves as a signal for macrophage attraction and activation, followed by the secretion of TGF-{beta} as a cytokine that is capable of terminally arresting Myc-driven lymphoma cells without causing further DNA damage and without launching a senescence-associated, pro-inflammatory, and, therefore, potentially detrimental cytokine response in the target population. In essence, non-cell-autonomous but still oncogene-orchestrated senescence is a functionally relevant, robustly tumor-suppressive principle with critical implications for conceptually novel anti-cancer therapies in the clinic.
Keywords:Apoptosis, Lymphoma, Macrophages, Mouse Models, Myc, Oncogenes, Senescence, TGF-{beta}
Source:Seminars in Cancer Biology
ISSN:1044-579X
Publisher:Elsevier / Academic Press (U.K.)
Volume:21
Number:6
Page Range:377-384
Date:December 2011
Official Publication:https://doi.org/10.1016/j.semcancer.2011.10.002
PubMed:View item in PubMed

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