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陈策实  研究员
肿瘤生物学学科组
职  务: 中科院、云南省动物模型和人类疾病机理重点实验室主任
学  历: 博士
电  话: +86 871 65181944
传  真: +86 871 65181945
电子邮件: chenc@mail.kiz.ac.cn
通讯地址: 云南省昆明市龙欣路17号 中国科学院昆明动物研究所肿瘤生物学实验室     650201
其他主页:
  简  历

博士生导师。从事肿瘤分子细胞生物学研究二十多年,在乳腺癌等肿瘤发现了多个重要癌症相关基因如KLF5WWP1HECTD3。并对它们遗传突变、作用与调节机制进行了深入系统研究,鉴定出一批新的候选靶标用于肿瘤临床诊治和预后以及新的抗癌药物筛选。近年来研究集中在蛋白质泛素化修饰与乳腺癌、KLF5和乳腺癌干细胞、乳腺癌动物模型、抗癌药物等。在Advanced SciJ Clin Invest.Nature Commun, Cancer Res等国际重要学术刊物发表了100多篇SCI论文,论文被SCI引用4900多次。申请人的H指数为40google scholar)。被国际会议和研究所邀请作报告400余次,同时被10多家机构邀请为基金评委(国家自然科学基金委和科技部等),担任Int J Bio SciCancer LettersCancer SciJBCJGGABBSZool Res和生命的化学编委,受邀为20多个SCI期刊审稿。培养博士后、博士研究生20多人。   

1990.9-1994.7 理学学士,南开大学生命科学院微生物系。 

1994.9-1999.6 理学博士,中科院上海生物工程研究中心和药物研究所。 

1999.6-2002.4 博士后,美国弗吉尼亚(Virginia)大学病理系。 

2002.4-2004.6 博士后,美国Emory 大学Winship 癌症研究所。 

2004.7-2005.12 讲师,美国Emory 大学Winship 癌症研究所。 

2006.1-2009.10 助理教授(Tenure Track),美国阿尔巴尼医学院细胞生物学癌症研究中心。 

2009.11-2010.5 副教授(Tenure Track),美国阿尔巴尼医学院细胞生物学和癌症研究中心 

2010.6-至今 研究员,博士生导师,中科院昆明动物研究所肿瘤生物学学科组负责人。

  研究方向

主要围绕乳腺癌发病机理进行深入的系统研究,对肿瘤遗传、蛋白质翻译后修饰、转录因子、细胞周期与凋亡、细胞迁移和癌症转移、信号传导、代谢、免疫、干细胞等方向感兴趣,在分子、细胞、模式动物和人等多个层次进行重要基因的功能及其机制研究,建立这些疾病的动物模型用于肿瘤预防与药物筛选。同时与多家医院展开合作,为预防和治疗人类癌症提供诊断/预后的分子标志物以及治疗靶标。目前分为四个方向: 

1. 蛋白质泛素化修饰与肿瘤 

蛋白质泛素化可以调节细胞周期,基因转录,DNA修复,迁移,以及凋亡等细胞过程。蛋白质泛素化需要三个酶相继催化完成,负责最后关键一步反应的酶叫做E3泛素连接酶,逆转泛素化修饰的酶叫去泛素化酶。我们发现很多E3DUB,如WWP1, Fbw7, HECTD3, RNF126, BCA2, BAP1,USP3等在乳腺癌中发生遗传和表达畸变。寻找、鉴定新的肿瘤相关的E3泛素连接酶和去泛素化酶,研究它们作用的分子机制,建立转基因动物模型,并开发它们在临床诊断和治疗的应用是我们主要的一个研究方向。 

2. KLF5转录因子与乳腺癌干细胞 

KLF5在基底型乳腺癌细胞中高表达。阳性KLF5的表达预示着病人生存时间短。我们多年的功能研究显示KLF5能紧密控制FGF-BP1mPGES1TNFAIP2Slug癌基因表达,然后促进细胞周期、生存和肿瘤生长和转移。KLF5的降解主要受到Fbw7WWP1的控制。Hippo信号通路的YAPTAZ共转录因子可以增加KLF5的稳定性和活性,从而促进乳腺癌细胞增殖和生存。KLF5的转录受到孕激素信号刺激后上调表达。我们发现乳腺特异性的KLF5 基因敲除小鼠乳腺发育延迟,我们将进一步研究KLF5在乳腺癌中的角色、下游调节基因、相互作用蛋白以及上游调节因子。希望能找到早期诊断预后标志物以及控制这条途径的药物。 

3. 乳腺癌动物模型 

目前的癌症动物模型绝大部分是用小鼠和大鼠模型。癌症的灵长类动物模型还没有建立。灵长类动物与人高度类似,我们通过研究大量树鼩自发乳腺癌我们发现PI3K/AKT信号途径过量活化,同时开展树鼩基础生物学研究。我们采用慢病毒表达PyMTPI3KCA癌基因以及抑制肿瘤抑制基因的方法建立可靠的树鼩肿瘤模型以及灵长类肿瘤模型,并进一步开发和评价肿瘤预防和治疗新方法。

4. 抗癌药物研发

针对抗癌药物靶点或细胞建立高通量筛选模型,对天然产物和小分子化合物库进行筛选,发现中药痛舒胶囊通过抑制ERa抑制乳腺细胞增殖,升麻提取物KHF16通过抑制NFkB信号通路抑制三阴性乳腺癌,避孕药米非司酮、二甲双胍、光辉霉素和超级增强子抑制剂通过抑制KLF5抑制三阴性乳腺癌干细胞。我们还对具有抗癌作用的先导化合物进行结构改造,优化生物活性,深入进行药理药效学研究,同时对外提供抗癌药物评价和药理研究服务。

  承担科研项目

项目名称 

所属计划 

经费 (万元) 

起止年月 

本人承担的任务 

上皮间质相互转换在乳腺(癌)干细胞中的功能、分子机制和应用研究

国家重点研发计划干细胞及转化研究重点专项

2889

2020.10-2025.1

首席科学家

KLF5转录因子作为基底型三阴性乳腺癌治疗靶点的研究

国家自然科学基金(NSFCs-云南省联合重点项目)

197

2017.1-2020.12

项目负责人 

蛋白精氨酸N端甲基化转移酶5PRMT5)促进乳腺细胞干性的功能和机制研究

国家自然科学基金面上项目

63

20181-2021.12

项目负责人 

E3泛素连接酶RNF126通过调节DNA损伤修复促进乳腺癌

国家自然科学基金重点项目

297

2019.1-2023.12

项目负责人 

  专家类别
研究员,杰青,万人计划领军人才,云岭学者
  社会任职
  获奖及荣誉

2018年 云南省自然科学三等奖(排名第1)

2018年 云岭学者

2018年 万人计划领军人才

2016年 科技部中青年科技创新领军人才

2016年 中科院特聘骨干人才

2015年 云南省科技进步一等奖(排名第5)

2013年 国家自然科学基金委杰出青年基金

2011年 中国科学院百人计划A类择优(海外杰出科学家)

2010年 云南省高端科技人才

2008年 美国癌症协会研究学者奖(Research Scholar Award from American Cancer Society)

  代表论著

*通讯作者) 

1. Benfu Zhong#, Dewei Jiang#, Yang Hong, Lifang Li, Li Qiu, Ronghui Yang, Xiaohan Jin, Yawen Song, Ceshi Chen*, Binghui Li*, Glucose-6-phosphate dehydrogenase neutralizes stresses by supporting reductive glutamine metabolism and AMPK activationSignal Transduction and Targeted Therapy2020, in press

2. Lina Zhao#, Ting Qiu#, Dewei Jiang#, Haibo Xu, Li Zou, Qin Yang, Ceshi Chen*, Baowei Jiao*, SGCE promotes breast cancer stem cells by stabilizing EGFR, Advanced Science, 2020, https://doi.org/10.1002/advs.201903700

3. Chao Dong#, Yin Chen#, Jing Ma#, Runxiang Yang#, Hongjian Li, Rong Liu, Dingyun You, Chunxiang Luo, Heng Li, Siyuan Yang, Kunbin Ke, Marie Chia-mi Lin*, Ceshi Chen*, Econazole nitrate reversed the resistance of breast cancer cells to Adriamycin through inhibiting the PI3K/AKT signaling pathway, American Journal of Cancer Research, 2020;10(1):263-274

4. Lingli He , Liang Yuan , Yang Sun , Pingyang Wang , Hailin Zhang , Xue Feng , Zuoyun Wang , Wenxiang Zhang , Chuanyu Yang , Yi Arial Zeng , Yun Zhao , Ceshi Chen*, Lei Zhang*, Glucocorticoid receptor signaling promotes breast cancer progression by activating TEAD4, Can Res, 2019, 79(17):4399-4411.

5. Yingying Wu, Qunying Qin , Fubing Li , Chuanyu Yang , Zhen Li , Zhongmei Zhou , Hailin Zhang , Yunxi Li , Xinye Wang , Rong Liu , Qian Tao , Wenlin Chen*, Ceshi Chen*, USP3 promotes breast cancer cell proliferation by deubiquitinating KLF5, J. Biol. Chem. 2019, 294(47)17837-47

6. Yanjie Kong*, Zehua Wang*, Maobo Huang, Zhongmei Zhou, Yi Li, Huilai Miao, Xing Wan, Jian Huang, Xiaoyun Mao#, Ceshi Chen#, CUL7 promotes cancer cell survival through promoting Caspase-8 ubiquitination, Int J Cancer, 2019

7. Chuan-Huizi Chen, Nong Yang, Yongchang Zhang, Jiancheng Ding, Wenjuan Zhang, Rong Liu, Wen Liu*, Ceshi Chen*, Inhibition of super enhancer downregulates the expression of KLF5 in basal-like breast cancers, Int J Biol. Sci., 2019; 15(8): 1733-1742.

8. Rong Liu*, Peiguo Shi, Zhongmei Zhou, Hailin Zhang, Ceshi Chen*, Krüpple-like factor 5 is Essential for Mammary Gland Development and Tumorigenesis, J Pathology, 2018, 246: 497-507

9. Huichun Liang#, Fei Ge#, Yuhui Xu#, Ji Xiao, Zhongmei Zhou, Rong Liu, Ceshi Chen, miR-153 inhibits the migration and the tube formation of endothelial cells by blocking the paracrine of angiopoietin 1 in breast cancer cells, Angiogenesis, (2018) 21:849–860.

10. Fubing Li#, Yang Li#, Huichun Liang#, Tao Xu#, Yanjie Kong, Chuanyu Yang, Maobo Huang, Zhongmei Zhou, Xiaomin Guo, Chunmiao Hu, Dongmei Zhou, Ceshi Chen*, Xiaopeng Qi*, HECTD3 mediates TRAF3 polyubiquitination and type I interferon induction during bacterial infection, J Clin Invest., 2018;128(9):4148-4162.

11. Huichun Liang, Ji Xiao, Zhongmei Zhou, Hailin Zhang, Zongcheng Li, Jian Sun, Fubing Li, Rong Liu*, and Ceshi Chen*, Hypoxia induces miR-153 through the IRE1α-XBP1 pathway to fine tune the HIF-1α/VEGFA axis in breast cancer angiogenesis, Oncogene, 2018, 37:1961-1975

12. Zekun Chen#, Qiuju Wu#, Ye Ding, Wenhui Zhou, Rong Liu, Haiying Chen, Jia Zhou*, Jing Feng*, Ceshi Chen*, YD277 Suppresses Triple-Negative Breast Cancer Partially Through Activating the Endoplasmic Reticulum Stress Pathway, Theranostics 2017; 7(8):2339-2349

13. Peiguo Shi, Wenjing Liu, Tala, Haixia Wang, Fubing Li, Hailin Zhang, Yingying Wu, Yanjie Kong, Zhongmei Zhou, Chunyan Wang, Wenlin Chen, Rong Liu, Ceshi Chen*, Metformin suppresses triple-negative breast cancer stem cells by targeting KLF5 for degradation, Cell Discovery, 2017, 3(17010)

14. Jing Wu, Ye Ding, Chuan-Hui zhi Chen, Zhongmei Zhou, Chunyong Ding, Haiying Chen, Jia Zhou*, Ceshi Chen*, A New Oridonin Analog Suppresses Triple-Negative Breast Cancer Cells and Tumor Growth via the Induction of Death Receptor 5. Cancer Letters, 2016, 380(2),393-402

15. Kong Y?, Li F?, Nian Y?, Zhou Z, Yang R*, Qiu MH*, Chen C*. KHF16 is a Leading Structure from Cimicifuga foetida that Suppresses Breast Cancer Partially by Inhibiting the NF-κB Signaling Pathway. Theranostics 2016; 6(6):875-886.

16. Rong Liu*, Peiguo Shi, Zhi Nie, Huichun Liang, Zhongmei Zhou, Wenlin Chen, Haijun Chen, Chao Dong, Runxiang Yang, Suling Liu, Ceshi Chen*Mifepristone Suppresses Basal Triple-Negative Breast Cancer Stem Cells by Down-regulating KLF5 ExpressionTheranostics 2016; 6(4): 533-544

17. Guang-Zhe Ge?, Hou-Jun Xia?, Bao-Li He, Hai-Lin Zhang, Wen-Jing Liu, Ming Shao, Chun-Yan Wang, Ji Xiao, Fei Ge, Fu-Bing Li, Yi Li, Ceshi Chen*, Generation and Characterization of a Breast Carcinoma Tree Shrew Model by PyMT Overexpression in Mammary Epithelial Cells, Int J Cancer, 20161383),642-651

18. Junying Qin, Zhongmei Zhou, Wenlin Chen, Chunyan Wang, Hailin Zhang, Guangzhe Ge, Ming Shao, Dingyun You, Zhixiang Fan, Houjun Xia, Rong Liu, Ceshi Chen* BAP1 promotes breast cancer cell proliferation and metastasis by deubiquitinating KLF5, Nature Communications, 2015, 6: 8471, doi:10.1038/ncomms9471

19. Lin Jia, Zhongmei Zhou, Huichun Liang, Jing Wu, Peiguo Shi, Fubing Li, Zehua Wang, Chunyan Wang, Wenlin Chen, Hailin Zhang, Yang Wang, Rong Liu, Jing Feng*, Ceshi Chen* KLF5 promotes breast cancer proliferation, migration and invasion in part by upregulating the transcription of TNFAIP2, Oncogene, 2015 Jul 20. doi: 10.1038/onc.2015.263.

20. Hou-Jun Xia, Bao-Li He, Chun-Yan Wang, Hai-Lin Zhang, Guang-Zhe Ge,  Yuan-Xu Zhang, Long-Bao Lv, Jian-Lin Jiao, Ceshi Chen*, PTEN/PIK3CA genes are frequently mutated in spontaneous and MPA-accelerated DMBA induced mammary tumours of tree shrews, Eur J Cancer, 2014, 50(18):3230-3242

21. Yi Li?, Yanjie Kong?, Zhongmei Zhou, Hui Chen, Zehua Wang, Yi-Ching Hsieh, Dong Zhao, Xu Zhi, Jian Huang, Jing Zhang, Hongmin Li, Ceshi Chen* The HECTD3 E3 Ubiquitin Ligase Facilitates Cancer Cell Survival by Promoting K63-linked Polyubiquitination of Caspase-8, Cell Death and Disease, 2013, 4, e935 

22. Xia H, Wang C, Chen W, Zhang H, Chaudhury L, Zhou Z, Liu R, Chen C*. Kruppel-Like Factor 5 Transcription Factor Promotes Microsomal Prostaglandin E2 Synthase 1 Gene Transcription in Breast Cancer. J Biol Chem. 2013 288(37):26731-40 

23. Zehua Wang, Zhi Nie, Wenlin Chen, Zhongmei Zhou, Qinghua Kong, Arun Seth, Rong Liu*, Ceshi Chen*RNF115/BCA2 E3 Ubiquitin Ligase Promotes Breast Cancer Cell Proliferation through Targeting p21 for Ubiquitin-mediated DegradationNeoplasia, 2013 15(9):1028-35 

24. Yi Li, Xi Chen, Zehua Wang, Dong Zhao, Hui Chen, Wenlin Chen, Zhongmei Zhou, Junran Zhang, Jing Zhang, Hongmin Li, Ceshi Chen*The HECTD3 E3 Ubiquitin Ligase Suppresses Cisplatin-induced Apoptosis via Stabilizing MALT1Neoplasia, 2013, 15(1)39-48 

25. Xu Zhi, Dong Zhao, Zehua Wang, Zhongmei Zhou, Chunyan Wang, Wenlin Chen, Rong Liu*, Ceshi Chen*, E3 ubiquitin ligase RNF126 promotes cancer cell proliferation by targeting the tumor suppressor p21 for ubiquitin-mediated degradation, Cancer Res. 2013;73(1):385-94 

26. Xu Zhi, Dong Zhao, Zhongmei Zhou, Rong Liu, Ceshi Chen*, YAP promotes breast cell proliferation and survival partially through stabilizing the KLF5 transcription factor, Am J Pathology, 2012, 180(6): 2452-61 

27. Dong Zhao, Xu Zhi, Zhongmei Zhou, Ceshi Chen*, TAZ antagonizes theWWP1-mediated KLF5 degradation and promotes breast cell proliferation and tumorigenesis, Carcinogenesis, 2012, 33(1): 59-67  

28. Rong Liu, Zhongmei Zhou, Dong ZhaoCeshi Chen*, The induction of KLF5 transcription factor by progesterone contributes to progesterone-induced breast cancer cell proliferation and de-differentiation, Mol. Endocrinology, 2011, 25(7): 1137-1144 (Cover)  

29. Rong Liu, Zhongmei Zhou, Jian Huang, Ceshi Chen*, PMEPA1 promotes androgen receptor negative prostate cell proliferation through suppressing the Smad3/4-c-Myc-p21Cip1 signaling pathway, Journal of Pathology, 2011, 223(5): 683-94 

30. Dong Zhao, Hanqiu Zheng, Zhongmei Zhou, Ceshi Chen*, The Fbw7 tumor suppressor targets KLF5 for ubiquitin-mediated degradation and suppresses breast cell proliferation, Cancer Research, 2010, 70: 4728-38  

31. Hanqiu Zheng, Zhongmei Zhou, Leena Chaudhury, Jin-Tang Dong, Ceshi Chen*, Krüpple-like factor 5 (KLF5) promotes breast cell proliferation partially through upregulating the transcription of fibroblast growth factor-binding protein 1 (FGF-BP) in breast cancer, Oncogene, 2009; 28: 3702-13. 

32. Rong Liu, Hanqiu Zheng, Zhongmei Zhou, Jin-Tang Dong, Ceshi Chen*, KLF5 promotes breast cell survival partially through FGF-BP-pERK-mediated MKP-1 protein phosphorylation and stabilization, J Biol Chem., 2009 19; 284: 16791-8 

33. Yi Li, Zhongmei Zhou, Maurizio Alimandi, Ceshi Chen*, WW domain containing E3 ubiquitin protein ligase 1 targets the full length ErbB4 for ubiquitin-mediated degradation in breast cancer, Oncogene, 2009 20; 28: 2948-58 

34. Yi Li, Zhongmei Zhou, Ceshi Chen*, WW domain containing E3 ubiquitin protein ligase 1 targets p63 transcription factor for ubiquitin-mediated proteasomal degradation and regulates apoptosis, Cell Death and Differentiation, 2008, 15: 1941-51 

  研究团队

工作人员:

蒋德伟 博士 副研究员,jiangdewei@mail.kiz.ac.cn

周忠梅 大专 实验师,zhouzm@mail.kiz.ac.cn

杨传雨 硕士 实验师,yangchuanyu@mail.kiz.ac.cn   

研究生:

王鑫晔;黄茂波;王海霞;刘文婧;杜光石;孙健;邱婷;程卓;任文龙;张红艳;江秋韵;曾丽;骆瑶;宋锦欢;王露珍;郑敏;李薇;甘文强;殷齐彦;陈雯敏;周陈钢;汪田甜

博士后:

孔燕杰;李富兵

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