代谢异常是癌症的一个重要标志。癌细胞即使在不缺氧的状态下也优先利用葡萄糖产生乳酸，这就是著名的瓦伯格效应（Warburg效应）。最近的癌症基因组学研究发现癌症的发生和发展与代谢异常有直接关系。目前一个涵盖癌症细胞内外的异常代谢特征网络正在形成， 而这些代谢特征是如何在肿瘤发生过程中形成且如何改变代谢进而导致癌症发生发展的机制还有很多尚未研究清楚。课题组长期从事营养与肿瘤代谢的研究工作，揭示了代谢物（营养组分）及酶可调控肿瘤细胞表观遗传和翻译后修饰，为可塑性代谢调控奠定理论基础，并以胰腺癌为突破口，系统阐明了代谢重塑在胰腺癌早期发生中的关键作用及其代谢靶向干预，指出了精准营养/饮食在肿瘤防治策略上的重要转化意义。课题组长雷群英作为项目主持人承担多项国家和省部级项目，包括国家自然科学基金创新研究群体项目、国家自然科学基金重大项目、重点项目、科技部国家重点基础研发计划和上海市教委重点项目等。迄今为止，已在国内外学术刊物上发表论文近60余篇，包括Cancer cell、Cell Metabolism、Molecular Cell、Nature Cell Biology、Nature Metabolism、National Science Review、Nature Communications、和 J.Clin. Invest.等。

代表论文

1.Qian L#, Li N#, Lu XC#, Xu MD#, Liu Y, Li KY, Zhang Y, Hu KW, Qi YT, Yao J, Wu YL, Wen WY, Huang SL, Chen ZJ, Yin M, Lei QY*. Enhanced BCAT1 activity and BCAA metabolism promotes RhoC activity in cancer progression. Nat Metab. 2023;5(7):1159-1173.

2.Li ML#, Cao SY, Qu J, Zhang L, Gao Q, Wang X, Yin M, Liu Y, Lei MZ*, Lei QY*.S-adenosyl-L-methionine supplementation alleviates damaged intestinal epithelium and inflammatory infiltration caused by Mat2a deficiency. Development. 2023; 150(20):dev201135. doi: 10.1242/dev.201135.

3.Ma QX#, Zhu WY, Lu XC, Jiang D, Xu F, Li JT, Zhang L, Wu YL, Chen ZJ, Yin M*, Huang HY*, Lei QY*. BCAA-BCKA axis regulates WAT browning through acetylation of PRDM16. Nat Metab. 2022;4(1):106-122.  Highlight in Nature Reviews Endocrinology

4.Huang W#, Li N#, Zhang Y, Wang X, Yin M, Lei QY*. AHCYL1 Senses SAH to Inhibit Autophagy through Interaction with PIK3C3 in an mTORC1-independent Manner. Autophagy, 2022;18(2):309-319.

5.Li JT#, Yang H#, Lei MZ#, Zhu WP#, Su Y, Li KY, Zhu WY, Wang J, Zhang L, Qu J, Lv L, Lu HJ, Chen ZJ, Wang L*, Yin M*, Lei QY*. Dietary folate drives methionine metabolism to promote cancer development by stabilizing MAT IIA. Signal Transduct Target Ther. 2022;7(1):192.

6.Pei X#, Li KY, Shen Y, Li JT, Lei MZ, Fang CY, Lu HJ, Yang HJ, Wen W, Yin M, Qu J*, Lei QY*. Palmitoylation of MDH2 by ZDHHC18 activates mitochondrial respiration and accelerates ovarian cancer growth. Sci China Life Sci. 2022;65(10):2017-2030.

7.Li JT#, Li KY#, Su Y, Shen Y, Lei MZ, Zhang F, Yin M, Chen ZJ, Wen WY, Hu WG, Su D*, Qu J*, Lei QY*. Diet High in Branched-chain Amino Acid Promotes PDAC Development by USP1-mediated BCAT2 Stabilization. National Science Review. 2021;9(5):nwab212.

8.Li JT#, Yin M#, Wang D#, Wang J, Lei MZ, Zhang Y, Liu Y, Zhang L, Zou SW, Hu LP, Zhang ZG, Wang YP, Wen WY, Lu HJ, Chen ZJ, Su D, Lei QY*. BCAT2-mediated BCAA Catabolism is Critical for Development of Pancreatic Ductal Adenocarcinoma. Nature Cell Biology, 2020; 22: 161-174.doi.org/10.1038/s41556-019-0455-6.  Highlight/Preview in Nature Cell Biology

9.Lei, M.-Z. #, Li, X.-X., Zhang, Y., Li, J.-T., Zhang, F., Wang, Y.-P., Yin, M., Qu, J. *, and Lei, QY.* Acetylation promotes BCAT2 degradation to suppress BCAA catabolism and pancreatic cancer growth. Signal transduction and targeted therapy, 2020; 5: 70.

10.Liu Y#, Guo JZ#, Liu Y#, Wang K, Ding WC, Wang H, Liu X, Zhou ST, Lu XC, Yang HB, Xu CY, Gao W, Zhou L, Wang YP, Hu WG, Wei YQ, Huang CH*, Lei QY*. Nuclear Lactate Dehydrogenase A Senses ROS to Produce a-Hydroxybutyrate for HPV-Induced Cervical Tumor Growth. Nature Commun.2018; 9: 4429.doi: 10.1038/s41467-018-06841-724.

11.Zhong XY#, Yuan XM, Xu YY, Yin M, Yan WW, Zou SW, Wei LM, Lu HJ, Wang YP*, Lei QY*. CARM1 Methylates GAPDH to Regulate Glucose Metabolism and Is Suppressed in Liver Cancer. Cell Rep. 2018; 24(12):3207-3223. doi: 10.1016/j.celrep.2018.08.066.

12.Xia S#, Lin R#, Jin L, Zhao L, Kang HB, Pan Y, Liu S, Qian G, Qian Z, Konstantakou E, Zhang B, Dong JT, Chung YR, Abdel-Wahab O, Merghoub T, Zhou L, Kudchadkar RR, Lawson DH, Khoury HJ, Khuri FR, Boise LH, Lonial S, Lee BH, Pollack BP, Arbiser JL, Fan J*, Lei QY*, Chen J*. Prevention of Dietary-Fat-Fueled Ketogenesis Attenuates BRAF V600E Tumor Growth. Cell Metabolism. 2017, 25(2):358-373.  Highlight in Nature

13.Zhang Y#, Xu YY#, Zhao XN, Li JT, Yang HB, Zhang M, Li, Yao CB, Yin M*, Chen J*, Lei QY*. Acetylation Targets HSD17B4 for Degradation via CMA Pathway in Response to E1. Autophagy. 2017, 13(3):538-553.

14.Wang YP*，Wang J，Gao X, Xu YY, Cheng JK*, Lei QY*. Arginine Methylation of MDH1 by CARM1 Inhibits Non-canonical Glutamine Metabolism and Suppresses Pancreatic Cancer. Molecular Cell. 2016, 64, 673–687.  Highlight in Cancer discovery

15.Gao X#, Lin SH#，Ren F, Li1 JT, Chen JJ, Yao CB,Yang HB,Jiang SX, Yan GQ, Wang D， Wang Y, Liu Y, Cai Z, Xu YY, Chen J, Yu W, Yang YP*, Lei QY*. Acetate Functions as an Epigenetic Metabolite to Promote Lipid Synthesis under Hypoxia. Nature Commun. 2016, 7: 11960. doi: 10.1038/ncomms11960.

16.Yang, HB#., Xu, YY#*., Zhao, XN, Zou SW*., Zhang Y., Zhang M., Li JT, Ren F., Wang LY., Lei QY*. Acetylation of MAT IIα represses tumour cell growth and is decreased in human hepatocellular cancer. Nature Commun. 2015, 6, 6973. doi: 10.1038/ncomms7973.

17.Zha, ZY. #, Han, XR., Matthew D. Smith, Liu, Y., Patrick M. Giguère, DraganaKopanja, PradipRaychaudhuri, David P. Siderovski, Guan, KL*., Lei, QY.*, and Xiong, Y*. A Non- canonical Function of Gβ as a Subunit of E3 Ligase in Targeting GRK2 Ubiquitylation. Molecular Cell. 2015; 58(5):794-803.

18.Zhou, X#., Wang, SY#., Wang, Z., Feng, X., Liu, P., Lv, X-B., Li, F-L., Yu, F-x., Sun,YP., Yuan, HX., Zhu, HG., Xiong,Y*., Lei, QY*., Guan, KL*. Estrogen Activates TAZ via GPER in Invasive Ductal Breast Carcinoma. J Clin Invest. 2015; 125(5):2123-35.

19.Zhao, D. #, Mo, Y., Li, MT., Zou, SW., Cheng, ZL., Sun, Y-P., Xiong, Y*., Guan, KL*., Lei, QY*. NOTCH-induced Aldehyde Dehydrogenase 1A1 Deacetylation Promotes Breast Cancer Stem Cells. J Clin Invest. 2014; 124(12):5453-65.

20.Li T, Liu F, Feng X, Wang Z, Das I, Xu Y, Zhou X, Sun Y, Guan KL, Xiong Y, Lei QY*. Glyceraldehyde-3-phosphate Dehydrogenase Is Activated by Lysine 254 Acetylation in Response to Glucose Signal. J. Biol. Chem. 2014; 289(6):3775-85.

21.Lv L#, Xu Y#, Zhao D, Li F, Wang W, Sasaki N, Jiang Y, Zhou X, Li T, Guan KL*, Lei QY*and Xiong Y*. Mitogenic and Oncogenic Stimulation of K433 Acetylation Promote PKM2 Protein Kinase Activity and Nuclear Localization. Molecular Cell. 2013; 52, 340–352.  Highlights: Cover story in Molecular cell, Nature Reviews in Cancer, and Cancer discovery

22.Lin R#, Ren T#, Gao X, Zhou X, Li T, Xiong Y, Guan KL, Lei QY*. Acetylation Stabilizes ATP- citrate Lyase to Promote Lipid Biosynthesis and Tumor Growth. Molecular Cell. 2013; 51, 506–518.

23.Zhao D#, Zou S#, Liu Y, Zhou X, Mo Y, Wang P, Xu Y, Dong B, Xiong Y*, Lei QY* and Guan KL*. Lysine-5 Acetylation Negatively Regulates Lactate Dehydrogenase A and Is Decreased in Pancreatic Cancer. Cancer Cell. 2013; 23, 464-476.

24.Lv L#, Li D, Zhao D, Lin R, Chu Y，Zhang H, Zha Z, Ying Liu, Li Z, Xu Y, Huang Y, Gang W, Xiong Y, Guan KL, and Lei QY*. Acetylation Targets the M2 Isoform of Pyruvate Kinase for Degradation through Chaperone-Mediated Autophagy and Promotes Tumor Growth. Molecular Cell. 2011; 42, 719-730.  Highlights: Feature article Preview in Molecular Cell, Science Signaling, and Faculty of 1000

邀请综/评述:

1.Zhang Y#, Lei MZ, Yin M, Lei QY*. A metabolic clue for STING suppression. Trends Cell Biol. 2023;S0962-8924(23)00077-6.

2.Yin M*, Lei QY*. BCAT2-BCKDH metabolon maintains BCAA homeostasis. Nat Metab. 2022 ;4(12):1618-1619.

3.Qian L#, Zhang F#, Yin M*, Lei QY*. Cancer metabolism and dietary interventions. Cancer Biology & Medicine.2021;19(2):163-74.

4.Wang YP*, Li JT, Qu J, Yin M, Lei QY*. (2020). Metabolite sensing and signaling in cancer. Journal of Biological Chemistry, 295(33), 11938-11946.

5.Li JT#, Wang YP, Yin M*, Lei QY*. (2019). Metabolism remodeling in pancreatic ductal adenocarcinoma. Cell Stress; 3(12):361-368.

6.Wang YP*, Lei QY*. (2018). Metabolite sensing and signaling in cell metabolism. Signal Transduction and Targeted Therapy; 3:30.

7.Zhou X#, Lei QY*. (2016). Regulation of TAZ in cancer. Protein & Cell; 7(8):548-61.

8.Zhou X#, Wang Z, Huang W, Lei QY*. (2015). G protein-coupled receptors: bridging the gap from the extracellular signals to the Hippo pathway. Acta Biochim Biophys Sin (Shanghai); (1):10-5.

9.Huang W#, Wang Z, Lei QY*. (2014). Acetylation control of metabolic enzymes in cancer: an updated version. Acta Biochim Biophys Sin (Shanghai); 46(3):204-13.

10.Lin R#, Zhou X, Huang W, Zhao D, Lv L, Xiong Y, Guan KL, Lei QY*. (2014). Acetylation control of cancer cell metabolism. Curr Pharm Des; (15):2627-33.

11.Zhao D#, Li FL, Cheng ZL, Lei QY*. (2014). Impact of acetylation on tumor metabolism. Mol Cell Oncol; 1(3):e963452.