2017年5月22日应重点实验室肿瘤生物学学科组陈策实研究员和肿瘤信号转导学科组陈勇彬研究员邀请，美国南阿拉巴马大学谭明教授应邀到所作了题为“Interplay between Immune Checkpoint Proteins and Cellular Metabolism”的学术报告。 

　　谭教授首先介绍了近年肿瘤免疫学的研究热点：免疫检查点（immune checkpoint modulators），包括著名的B7家族蛋白。前期研究表明它们能够调控细胞免疫，肿瘤能量代谢、微环境和代谢重编程等。谭教授团队发现B7家族免疫调控蛋白成员之一的B7-H3也参与肿瘤细胞代谢。 

　　B7-H3（又名CD276）是B7家族的最新成员，其氨基酸端有一信号肽，包括细胞外的免疫球蛋白样可变区（IgV）和恒定区(IgC)，B7-H3的 mRNA广泛表达，而B7-H3蛋白仅仅表达在树突状细胞，在其它正常组织中不表达。谭教授课题组发现B7-H3蛋白在多个肿瘤组织中广泛过表达，参与肿瘤代谢和生长，尤其在乳腺癌中有高达80%的阳性率，在乳腺癌中调控迁移、侵袭、凋亡和能量代谢，并且参与耐药相关信号通路调控，因此能作为癌症诊断的候选生物标志物和治疗靶标。 

　　随后，谭教授详细讲解了B7-H3在促进乳腺癌能量代谢中的功能和机制。B7-H3是一个促进癌细胞有氧酵解、抑制线粒体途径的新型蛋白，通过激活ROS介导的HIF-1α稳定，促进Warburg效应；同时抑制转录因子Nrf2的入核，来促进乳腺癌细胞的增殖以及小鼠移植瘤模型的葡萄糖摄取量。这一研究成果奠定了B7-H3作为潜在癌症治疗靶点的基础，把免疫检查点蛋白和肿瘤代谢关联起来。 

　　这一精彩的报告让在场的师生耳目一新，陈策实和焦保卫等研究员结合昆明动物所的灵长类资源等与谭教授进行了细致讨论与展望。报告最后在大家的热烈讨论中结束。 

　　（图一：谭教授给大家作报告） 

　　（图二：听众认真听报告）

　　（图三：听众和谭教授讨论） 

　　专家简介： 

　　谭明博士，1988年毕业于华西医科大学，获法医遗传学硕士学位。2000年获MD Anderson Cancer Center肿瘤生物学博士学位，随后5年在该医学中心从事博士后训练。2007-2011年期间担任南阿拉巴马大学助理教授，现任该校Mitchell癌症研究所终身副教授，细胞死亡和代谢研究中心首席科学家，肿瘤生物学中心主任。曾在Mol Cell，Mol Cell Biol，Cancer Cell，Mol Cancer，Cancer Res，Oncogene，J BiolChem和Cell Death Dis等多个SCI杂志发表研究成果。 

　　Contribution to Science： 

　　Oncogenic reprograming of cancer cell glucose metabolism: We found that oncogene ErbB2 overexpression leads to dysregulated cell metabolism by upregulate heat shock factor 1/LDHA, and targeting ErbB2 mediated dysregulation of glucose metabolism can overcome therapeutic resistance. 

　　1.     Lim S, Phillips J,  Madeira da Silva L, Zhou M, Fodstad O, Owen LB, and Tan M. Interplay between Immune Checkpoint Proteins and Cellular Metabolism. Cancer Res. 2017 In Press, NIHMS845079. 

　　2.     Zhao YH, Zhou M, Liu H, KhongHT, Yu DH, Fodstad O, and Tan M. Upregulation of LDH-A by ErbB2 through HSF1 promotes breast cancer cell glycolysis and growth. Oncogene, 28(42):3689-701, 2009. PMID:19668225. 

　　3.    Zhao Y, Liu H, Liu Z, Ding Y, LeDouxSP, Wilson GL, Voellmy R, Lin Y, Lin W, Nahta R, Liu B, Fodstad O, Chen J, Wu Y, Price JE, and Tan M. Overcoming Trastuzumab Resistance in ErbB2-Positive Breast Cancer by Targeting Dysregulated Glucose Metabolism. Cancer Res,71(13):4585-97, 2011. PMID: 21498634, PMCID:PMC3129363. 

　　4.     Butler, E.B., Zhao, Y., Mu？oz Pinedo, C., Lu, J., and Tan, M. Stalling the engine of resistance: targeting cancer metabolism to overcome therapeutic resistance (Invited Review). Cancer Res, 73(9):2709-17, 2013. PMID: 23610447, PMCID: PMC3644012. 

　　HSF1 in cancer cell stress responsive signaling: We investigated the role of stress signals such as ROS, Heat Shock Factor 1 (HSF1) in cancer cell stress response and in drug resistance. We found that ROS plays an important role in cancer cell drug resistance and HSF1 can transcriptionally regulate ATG7 and autophagy and controls cancer cell chemosensitivity. 

　　1.     Zhou M, Zhao YH, Liu H, Ding Y, Fodstad O, Riker AI, Owen LB, LeDouxSP and Tan M. Targeting LDH-A re-sensitizes Taxol-resistant breast cancer cells to Taxol. Mol Cancer, 9(1):33, 2010. PMCID:PMC2829492. 

　　2.     Kamarajugadda S, Stemboroski L, Cai Q, Simpson NE, Nayak S, Tan M, Lu JR. Glucose Oxidation Modulates Anoikis and Tumor Metastasis.(2012)  Mol Cell Biol. 32:1893-907, 2012. PMID:22431524, PMCID:PMC3347404. 

　　3.     Desai S, Liu Z, Yao J, Patel N, Chen J, Wu Y, Ahn EE, Fodstad O, Tan M. Heat Shock Factor 1 (HSF1) controls chemoresistance and autophagy through transcriptional regulation of Autophagy -related Protein 7 (ATG7). J Biol Chem. 288(13):9165-76, 2013. PMID: 23386620, PMCID: PMC3610989. 

　　4.     Zhao Y, Butler EB, Tan M. Targeting cellular metabolism to improve cancer therapeutics. Cell Death Dis. 4:e532, 2013. PubMed PMID: 23470539; PubMed Central PMCID: PMC3613838. 

　　Non-coding RNA and cancer stem cells in cancer therapeutic resistance: We are one of the first research groups to investigate the role of microRNAs in cancer resistance to chemotherapeutic agents. We find that miR-125b regulate Taxol-induced apoptosis through directly target BAK1 in breast cancer cells. In addition, miR-125b overexpression leads to cancer stem cell enrichment, which also contributes to miR-125b mediated therapeutic resistance.  

　　5.     Zhou M, Zhao YH, Ding Y, Liu H, Liu Z, Xi Y, Xiong W, Li GY, Lu JR, Fodstad O, Riker AI, and Tan M. MicroRNA-125b confers the resistance of breast cancer cells to paclitaxel through suppression of Bak1 expression. J BiolChem, 285: 28. 21496-507, 2010. PMCID:PMC2898411. 

　　6.     Huang J, Townsend C, Dou D, Liu H, Tan M. OMIT: a domain-specific knowledge base for microRNA target prediction. Pharm Res. 2011 Dec;28(12):3101-4. PubMed PMID: 21879385. 

　　7.     Zixing Liu, Hao Liu, Shruti Desai, David Schmitt, Hung T. Khong, Kristine S. Klos, Steven McClellan, OysteinFodstad, and Ming Tan.  Upregulation of MicroRNA-125b through Wnt signaling by Snail Enriches Cancer Stem Cells and Increases Chemoresistance. J BiolChem, 288(6):4334-45, 2013. PMID: 23255607, PMCID: PMC3567684. 

　　8.     Schmitt DC, Madeira da Silva L, Zhang W, Liu Z, Arora R, Lim S, Schuler AM, McClellan S, Andrews JF, Kahn AG, Zhou M, AhnEY, Tan M. ErbB2-intronic microRNA-4728: a novel tumor suppressor and antagonist of oncogenic MAPK signaling. Cell Death Dis. 6:e1742, 2015. PubMed PMID: 25950472, PMCID: in process. 

　　ErbB2 and its downstream signaling regulated cancer cell progression and drug resistance: We investigated the role of ErbB2 and its downstream signaling molecules such as Akt, HIF1a, and STAT3 in tumor progression and drug resistance. We also used TAT sequence to target a STAT3 inhibiting peptides to inhibit tumor growth in animal models. 

　　9.     Tan M, Jing T, Lee S, LanKH, Li P, Nagata Y, Liu J, Arlinghaus R, Hung MC, and Yu D. Direct Phosphorylation on Tyrosine-15 of p34Cdc2 by erbB2 Receptor Tyrosine Kinase Inhibits p34Cdc2 Activation. Mol Cell, 9:993-1004, 2002. PMID:12049736. 

　　10.   Nagata Y, LanKH, Zhou X, Tan M, EstevaFJ, Sahin AA, Klos KS, Li P, Monia BP, Nguyen NT, HortobagyiGN, Hung MC, and Yu D. PTEN Activation Contributes to Tumor Inhibition by Trastuzumab and Loss of PTEN Predicts Trastuzumab Resistance in Patients. Cancer Cell, 6:117-21, 2004 PMID:15324695. 

　　11.   Li YM, Pan Y, Wei Y, Cheng X, Zhou BP, Tan M, Zhou X, Xia W, HortobagyiGN, Yu D, Hung MC. Upregulation of CXCR4 is essential for HER2-mediated tumor metastasis. Cancer Cell. 2004 Nov;6(5):459-69. PubMed PMID: 15542430. 

　　12.   Tan M, LanKH, Yao J, Lu CH, Sun M, et al. Selective inhibition of ErbB2-overexpressing breast cancer in vivo by a novel TAT-based ErbB2-targeting signal transducers and activators of transcription 3-blocking peptide. Cancer Res. 66(7):3764-72, 2006. PubMed PMID: 16585203