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| Item Type: | Review |
|---|---|
| Title: | The Myc/macrophage tango: Oncogene-induced senescence, Myc style |
| Creators Name: | Lee, S., 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 |
| 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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