Other
19 Authors
- Jing H,
- Green MR,
- Hong JY,
- Shen H,
- Jain N,
- Wang L,
- Lyssiotis CA,
- Mistry SJ,
- Chiang YL,
- Cantley LC,
- Cross JR,
- Hu J,
- Chen Z,
- Li M,
- Lin H,
- Duy C,
- Cerchietti L,
- Teater MR,
- Melnick AM
| First Author | Li M | Year | 2019 |
| Journal | Cancer Cell | Volume | 35 |
| Issue | 6 | Pages | 916-931.e9 |
| PubMed ID | 31185214 | Mgi Jnum | J:276358 |
| Mgi Id | MGI:6314532 | Doi | 10.1016/j.ccell.2019.05.002 |
| Citation | Li M, et al. (2019) Non-oncogene Addiction to SIRT3 Plays a Critical Role in Lymphomagenesis. Cancer Cell 35(6):916-931.e9 |
| abstractText | Diffuse large B cell lymphomas (DLBCLs) are genetically heterogeneous and highly proliferative neoplasms derived from germinal center (GC) B cells. Here, we show that DLBCLs are dependent on mitochondrial lysine deacetylase SIRT3 for proliferation, survival, self-renewal, and tumor growth in vivo regardless of disease subtype and genetics. SIRT3 knockout attenuated B cell lymphomagenesis in VavP-Bcl2 mice without affecting normal GC formation. Mechanistically, SIRT3 depletion impaired glutamine flux to the TCA cycle via glutamate dehydrogenase and reduction in acetyl-CoA pools, which in turn induce autophagy and cell death. We developed a mitochondrial-targeted class I sirtuin inhibitor, YC8-02, which phenocopied the effects of SIRT3 depletion and killed DLBCL cells. SIRT3 is thus a metabolic non-oncogene addiction and therapeutic target for DLBCLs. |
