Non-oncogene Addiction to SIRT3 Plays a Critical Role in Lymphomagenesis

被引：92

作者：

Li, Meng ^{[1
]}

Chiang, Ying-Ling ^{[2
]}

Lyssiotis, Costas A. ^{[3
]}

Teater, Matthew R. ^{[1
]}

Hong, Jun Young ^{[2
]}

Shen, Hao ^{[1
]}

Wang, Ling ^{[1
]}

Hu, Jing ^{[2
]}

Jing, Hui ^{[2
]}

Chen, Zhengming ^{[4
]}

Jain, Neeraj ^{[7
]}

Duy, Cihangir ^{[1
]}

Mistry, Sucharita J. ^{[1
]}

Cerchietti, Leandro ^{[1
]}

Cross, Justin R. ^{[5
]}

Cantley, Lewis C. ^{[6
]}

Green, Michael R. ^{[7
]}

Lin, Hening ^{[2
,8
]}

Melnick, Ari M. ^{[1
]}

机构：

[1] Weill Cornell Med, Dept Med, Div Hematol & Med Oncol, New York, NY 10065 USA

[2] Cornell Univ, Dept Chem & Chem Biol, Ithaca, NY 14853 USA

[3] Univ Michigan, Dept Mol & Integrat Physiol, Med Sch, Ann Arbor, MI 48109 USA

[4] Weill Cornell Med, Div Biostat & Epidemiol, New York, NY 10021 USA

[5] Mem Sloan Kettering Canc Ctr, Canc Biol & Genet Program, New York, NY 10065 USA

[6] Weill Cornell Med, Meyer Canc Ctr, New York, NY 10065 USA

[7] Univ Texas MD Anderson Canc Ctr, Dept Lymphoma Myeloma, Houston, TX 77005 USA

[8] Cornell Univ, Howard Hughes Med Inst, Ithaca, NY 14853 USA

来源：

CANCER CELL | 2019年 / 35卷 / 06期

关键词：

GERMINAL CENTER FORMATION; GENE-EXPRESSION; ANTITUMOR-ACTIVITY; CELL; AUTOPHAGY; CANCER; METABOLISM; INHIBITOR; SURVIVAL; REVEALS;

D O I：

10.1016/j.ccell.2019.05.002

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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.

引用

页码：916 / +

页数：25

共 79 条

[21] STAR: ultrafast universal RNA-seq aligner [J].

Dobin, Alexander ;

Davis, Carrie A. ;

Schlesinger, Felix ;

Drenkow, Jorg ;

Zaleski, Chris ;

Jha, Sonali ;

Batut, Philippe ;

Chaisson, Mark ;

Gingeras, Thomas R. .

BIOINFORMATICS, 2013, 29 (01) :15-21

[22] VavP-Bcl2 transgenic mice develop follicular lymphoma preceded by germinal center hyperplasia [J].

Egle, A ;

Harris, AW ;

Bath, ML ;

O'Reilly, L ;

Cory, S .

BLOOD, 2004, 103 (06) :2276-2283

[23] Nucleocytosolic Depletion of the Energy Metabolite Acetyl-Coenzyme A Stimulates Autophagy and Prolongs Lifespan [J].

Eisenberg, Tobias ;

Schroeder, Sabrina ;

Andryushkova, Aleksandra ;

Pendl, Tobias ;

Kuettner, Victoria ;

Bhukel, Anuradha ;

Marino, Guillermo ;

Pietrocola, Federico ;

Harger, Alexandra ;

Zimmermann, Andreas ;

Moustafa, Tarek ;

Sprenger, Adrian ;

Jany, Evelyne ;

Buettner, Sabrina ;

Carmona-Gutierrez, Didac ;

Ruckenstuhl, Christoph ;

Ring, Julia ;

Reichelt, Wieland ;

Schimmel, Katharina ;

Leeb, Tina ;

Moser, Claudia ;

Schatz, Stefanie ;

Kamolz, Lars-Peter ;

Magnes, Christoph ;

Sinner, Frank ;

Sedej, Simon ;

Froehlich, Kai-Uwe ;

Juhasz, Gabor ;

Pieber, Thomas R. ;

Dengjel, Joern ;

Sigrist, Stephan J. ;

Kroemer, Guido ;

Madeo, Frank .

CELL METABOLISM, 2014, 19 (03) :431-444

[24] Germinal Center Selection and Affinity Maturation Require Dynamic Regulation of mTORC1 Kinase [J].

Ersching, Jonatan ;

Efeyan, Alejo ;

Mesin, Luka ;

Jacobsen, Johanne T. ;

Pasqual, Giulia ;

Grabiner, Brian C. ;

Dominguez-Sola, David ;

Sabatini, David M. ;

Victora, Gabriel D. .

IMMUNITY, 2017, 46 (06) :1045-+

[25] SIRT3 Opposes Reprogramming of Cancer Cell Metabolism through HIF1α Destabilization [J].

Finley, Lydia W. S. ;

Carracedo, Arkaitz ;

Lee, Jaewon ;

Souza, Amanda ;

Egia, Ainara ;

Zhang, Jiangwen ;

Teruya-Feldstein, Julie ;

Moreira, Paula I. ;

Cardoso, Sandra M. ;

Clish, Clary B. ;

Pandolfi, Pier Paolo ;

Haigis, Marcia C. .

CANCER CELL, 2011, 19 (03) :416-428

[26] A critical role of autophagy in antileukemia/lymphoma effects of APO866, an inhibitor of NAD biosynthesis [J].

Ginet, Vanessa ;

Puyal, Julien ;

Rummel, Coralie ;

Aubry, Dominique ;

Breton, Caroline ;

Cloux, Anne-Julie ;

Majjigapu, Somi R. ;

Sordat, Bernard ;

Vogel, Pierre ;

Bruzzone, Santina ;

Nencioni, Alessio ;

Duchosal, Michel A. ;

Nahimana, Aimable .

AUTOPHAGY, 2014, 10 (04) :603-617

[27] Transient expression of Bcl6 is sufficient for oncogenic function and induction of mature B-cell lymphoma [J].

Green, Michael R. ;

Vicente-Duenas, Carolina ;

Romero-Camarero, Isabel ;

Liu, Chih Long ;

Dai, Bo ;

Gonzalez-Herrero, Ines ;

Garcia-Ramirez, Idoia ;

Alonso-Escudero, Esther ;

Iqbal, Javeed ;

Chan, Wing C. ;

Campos-Sanchez, Elena ;

Orfao, Alberto ;

Pintado, Belen ;

Flores, Teresa ;

Blanco, Oscar ;

Jimenez, Rafael ;

Angel Martinez-Climent, Jose ;

Garcia Criado, Francisco Javier ;

Garcia Cenador, Maria Begona ;

Zhao, Shuchun ;

Natkunam, Yasodha ;

Lossos, Izidore S. ;

Majeti, Ravindra ;

Melnick, Ari ;

Cobaleda, Cesar ;

Alizadeh, Ash A. ;

Sanchez-Garcia, Isidro .

NATURE COMMUNICATIONS, 2014, 5

[28] Integrative Genomic Profiling Reveals Conserved Genetic Mechanisms for Tumorigenesis in Common Entities of Non-Hodgkin's Lymphoma [J].

Green, Michael R. ;

Aya-Bonilla, Carlos ;

Gandhi, Maher K. ;

Lea, Rod A. ;

Wellwood, Jeremy ;

Wood, Peter ;

Marlton, Paula ;

Griffiths, Lyn R. .

GENES CHROMOSOMES & CANCER, 2011, 50 (05) :313-326

[29] Autophagy variation within a cell population determines cell fate through selective degradation of Fap-1 [J].

Gump, Jacob M. ;

Staskiewicz, Leah ;

Morgan, Michael J. ;

Bamberg, Alison ;

Riches, David W. H. ;

Thorburn, Andrew .

NATURE CELL BIOLOGY, 2014, 16 (01) :47-+

[30] SIRT3 Is a Mitochondrial Tumor Suppressor: A Scientific Tale That Connects Aberrant Cellular ROS, the Warburg Effect, and Carcinogenesis [J].

Haigis, Marcia C. ;

Deng, Chu-Xia ;

Finley, Lydia W. S. ;

Kim, Hyun-Seok ;

Gius, David .

CANCER RESEARCH, 2012, 72 (10) :2468-2472

← 1 2 3 4 5 6 7 8 →