柳满然，男，1966年出生，理学博士，巴渝学者特聘教授。

Manran Liu（1966.05～）,Doctor of Science,Professor,Doctor Adviser

1992年助理研究员、讲师，2009年教授，2010年博士生导师；

联系信息：

重庆医科大学，检验医学院/临床检验诊断学教育部重点实验室，400016

Tel/Fax, +86-23-68485938; E-mail, 1293390832@qq.com;mliu-hncq@hotmail.com

学习（进修）与工作经历

1984.9～1988.7，湖南师范大学生物系，生物学学士；

1989.9～1991.7，山东大学生物系，生态学硕士；

1991.7～1995.9，中国科学院青岛海洋所，助理研究员；

1995.10～1999.9，青岛大学医学院，讲师。

1999.9～2002.7，北京大学医学部临床肿瘤学院，肿瘤生化与分子生物专业，博士；

2003.2～2005.10，Department of Oncology, Lombardi Comprehensive Cancer Center (LCC), Georgetown University, Washington, USA. Postdoctoral Fellow (Supervisor: Professor Richard G. Pestell)；

2005.11～2008.11，Department of Oncology, Kimmel Cancer Center (KCC), Thomas Jefferson University, Philadelphia, USA. Instructor, Assistant Professor (Supervisor: Professor Richard G. Pestell)；

2009.6～至今，重庆医科大学基础医学院，检验医学院，临床检验诊断学教育部重点实验室；

荣誉和奖励

2015年获重庆医科大学优秀科技奖

2016年入选重庆市“巴渝学者”特聘教授

2020年获重庆市科学技术奖（自然科学）二等奖

学术兼职

重庆市生物化学与分子生物学会理事，中国细胞生物学学会会员

Cnacer Res, Mol Oncology, Mol Cellular Pathology, Amer J Pathology, PLoS One, Cellular Signaling等杂志审稿人

研究方向：肿瘤信号传导异常、肿瘤微环境与肿瘤转移、肿瘤干细胞、肿瘤代谢及其药物耐受

长期从事肿瘤细胞信号传导异常与肿瘤起始与转移、肿瘤干细胞方面的研究；近年来以肿瘤微环境为研究对象，研究肿瘤微环境对肿瘤转移、肿瘤代谢、肿瘤药物耐受的影响，探寻其分子生物机制。并针对肿瘤细胞信号传导的重要节点，进行靶向干预；以影响肿瘤细胞的主要信号传导基因、肿瘤代谢产物为重点，筛选肿瘤相关分子标志。具体涉及如下研究内容：

(1)肿瘤信号传导异常与EMT、肿瘤干细胞聚集的调控分子机制：既往研究主要针对肿瘤细胞重要信号传导途径，研究其与EMT转化、肿瘤转移关系和分子生物机制。归国以来，主要利用芯片与蛋白组学技术为基础，以生物信息学分析为手段，挖掘影响EMT转化、EMT相关肿瘤干细胞聚集、自我更新等方面的分子机制研究。

(2)肿瘤微环境中肿瘤相关成纤维细胞为重点，研究肿瘤微环境特征、ECM变化等对癌细胞浸润、药物耐受的影响和分子生物机制。

(3)基于前期工作积累，近年来拓展了肿瘤代谢、肿瘤微环境基质细胞代谢对癌细胞浸润、药物耐受的影响和分子生物机制研究；

作为负责人主持的科研项目

2010.1-2010.12，国家自然科学基金“ER+和ER-乳腺癌微环境中CAF细胞基因表达与信号通路变化的初步研究”，编号30940096；

2011.1-2013.12，国家自然科学基金“miRNA促进乳腺微环境成纤维细胞向CAF转化及机理研究”，编号 81072147；

2012.1-2015.12，国家自然科学基金“Twist调控乳腺上皮细胞EMT转化及肿瘤干细胞样细胞特征的机制研究”，编号31171336；

2015.1-2018.12，国家自然科学基金“低氧诱导的氧化型ATM调节乳腺癌CAFs能量代谢重塑的机理及其促乳腺癌侵袭转移研究”，编号81472476；

2011.1-2013.12，重庆市科委项目“c-ski对乳腺癌微环境CAF活化的影响”，编号CSTC 2010BB5099；

2011.1-2013.12，教育部归国留学专项科研基金“乳腺肿瘤微环境中CAF细胞基因表达与信号通路变化的初步研究”，批文号：教外司[2011]508号；

2011.1-2013.12，教育部博士点专项科研基金“miRNA调控乳腺肿瘤微环境CAF活化与功能研究”，编号20105503110001；

2013.1-2015.12，教育部博士点专项科研基金“Twist促进乳腺肿瘤干细胞聚集的关键miRNAs和细胞信号通路研究”，编号20125503110001；

此外，作为学术带头人，组建了肿瘤基础与临床研究团队，近6年来带领团队获得了10项国家自然科学基金（其中以课题负责人获得5项）。

作为通讯作者或论文指导者发表的主要论文

2015年

1.Xi Tang*, Yixuan Hou, Guanglun Yang, Xing Wang, Shifu Tang, Yan-e Du, Li Yang, Tenghua Yu, Hailong Zhang, Mingli Zhou, Siyang Wen, Liyun Xu, Manran Liu#. Stromal miR-200s contribute to breast cancer cell invasion through CAF activation and ECM remodeling. Cell death and Differenciation 2015; in press, doi: 10.1038/cdd.2015.78. (IF 8.184).

2.Li Yang*, Yixuan Hou*, Jie Yuan, Shifu Tang, Hailong Zhang, Qing Zhu, Yan-e Du, Mingli Zhou, Siyang Wen, Liyun Xu, Xi Tang, Xiaojiang Cui, Manran Liu#. Twist promotes reprogramming of glucose metabolism in breast cancer cells through PI3K/AKT and p53 signaling pathways. Oncotarget 2015; in press (IF 6.359).

3.Mingli Zhou*, Yixuan Hou*, Guanglun Yang, Hailong Zhang, Gang Tu, Yan-e Du, Siyang Wen, Liyun Xu, Xi Tang, Shifu Tang, Li Yang, Xiaojiang Cui, Manran Liu#. LncRNA-Hh strengthen cancer stem cells generation in Twist-positive breast cancer via activation of Hedgehog signaling pathway. Stem Cell 2015; in press (IF 6.532).

4.Shifu Tang*, Yixuan Hou, Hailong Zhang, Gang Tu, Li Yang, Yifan Sun, Lei Lang, Xi Tang, Yan-e Du, Mingli Zhou, Tenghua Yu, Liyun Xu, Siyang Wen, Chunming Liu, Manran Liu#. Oxidized ATM promotes the abnormal proliferation of breast CAF through keeping intracellular redox homeostasis and activating the PI3K-AKT, ERK-MAPK, and Wnt signaling pathways. Cell Cycle, 2015; 14(12):1908-24. (IF 4.565).

5.Jie Yuan*, Manran Liu*, Li Yang*, Gang Tu, Qing Zhu, Maoshan Chen, Hong Cheng, Haojun Luo, Weijie Fu, Zhenhua Li, Guanglun Yang#. Acquisition of epithelial-mesenchymal transition phenotype in the tamoxifen-resistant breast cancer cell: a new role for Gprotein-coupled estrogen receptor in mediating tamoxifen resistance through Cancer-associated fibroblast-derived fibronectin and β1-integrin signaling pathway in tumor cells. Breast Cancer Res 2015, 17:69, doi: 10.1186/s13058-015-0579-y. in press (IF 5.49).

6.Haojun Luo*, Gang Tu, Zhiming Liu, Manran Liu#. Cancer-associated fibroblasts: a multifaced driver of breast cancer progression. Cancer Lett 2015; 361(2):155-63. (IF 5.621).

2014年

7.Shifu Tang*, Li Yang, Xi Tang, Manran Liu#. The role of oxidized ATM in the regulation of oxidative stress-induced energy metabolism reprogramming of CAFs. Cancer Lett 2014; 353(2):133-44. (IF 5.1).

8.Tenghua Yu*, Manran Liu, Haojun Luo,Chengyi Wu, Xi Tang, Shifu Tang, Ping Hu, Yuzhao Yan, Zhiliang Wang, Gang Tu#. GPER mediates enhanced cell viability and motility via non-genomic signaling induced by 17b-estradiol in triple-negative breast cancer cells. J Steroid Biochem Mol Biol 2014, 143:392-403. (IF 4.1).

9.Haojun Luo*, Guanglun Yang, Tenghua Yu, Shujuan Luo, Chengyi Wu, Yan Sun, Manran Liu# and Gang Tu#. GPER-mediated proliferation and estradiol production in breast cancer-associated fibroblasts. Endocrine-Related Cancer 2014; 23: 355-69. (IF 5.09).

10.Liuyang Zhao*, Na Yu*, Tianfang Guo, Yixuan Hou, Zongyue Zeng, Xiaorong Yang, Ping Hu, Xi Tang, Jian Wang, and Manran Liu#. Tissue Biomarkers for Prognosis of Prostate Cancer: A Systematic Review and Meta-analysis. Cancer Epidemiology, Biomarkers Prevention 2014, 23(6):1047-54. (IF 4.6)

11.Ping Hu*, JiajiaYang, Yixuan Hou, Hailong Zhang, Zongyue Zeng, Liuyang Zhao, Tenghua Yu, Xi Tang, Gang Tu, Xiaojiang Cui, Manran Liu#. LncRNA expression signatures of twist-induced epithelial-to-mesenchymal transition in MCF10A cells. Cellular Signaling 2014, 26(1): 83-93. (IF 4.6)

12.Xin Yang*, Zongyue Zeng, Yixuan Hou, Taixian Yuan, Chao Gao, Wei Jia, Xiaoyan Yi, Manran Liu#. MicroRNA-92a as a Potential Biomarker in Diagnosis of Colorectal Cancer: A Systematic Review and Meta-Analysis. PLoS ONE 2014, 9(2), e88745:1-7. (IF 3.75).

13.Xiaoli Tang*, Dong Zheng*, Ping Hu, Zongyue Zeng, Ming Li, Lynne Tucker, Renee Monahan, Murray B. Resnick, Manran Liu, and Bharat Ramratnam. Glycogen synthase kinase 3 beta inhibits microRNA-183-96-182 cluster via the β-Catenin/TCF/LEF-1 pathway in gastric cancer cells. Nucleic Acids Res 2014, 42(5):2988-98. (IF 8.3).

2013年

14.Liyang Wang*, Yixuan Hou*, Yan Sun, Liuyang Zhao, Xi Tang, Ping Hu, Jiajia Yang, Zongyue Zeng, Guanglun Yang, Xiaojiang Cui, Manran Liu#. c-Ski activates cancer-associated fibroblasts to regulate breast cancer cell invasion. Mol Oncology 2013, 7(6):1116-28. (IF 5.96).

15.Qiongle Peng*, Liuyang Zhao*, Yixuan Hou, Yan Sun, Liyang Wang, Haojun Luo, Huimin Peng, Manran Liu#. Biological characteristics and genetic heterogeneity between carcinoma-associated fibroblasts and their paired normal fibroblasts in human breast cancer. PLoS ONE. 2013, 8(4):e60321. (IF 4.1).

16.Zhiqiang Mo*, Manran Liu, Fangfang Yang, Haojun Luo, Zhenhua Li, Gang Tu# and Guanglun Yang#. GPR30 as an initiator of tamoxifen resistance in hormone-dependent breast cancer. Breast Cancer Res 2013, 15(6):R114. (IF 5.87).

2012年

17.Liuyang Zhao*, Yan Sun*, Yixuan Hou, Qiongle Peng, Liyang Wang, Haojun Luo, Xi Tang, Zongyue Zeng, Manran Liu#. MiRNA expression analysis of cancer-associated fibroblasts and normal fibroblasts in breast cancer. Int J Biochem Cell Biol 2012, 44(11):2051-9. (IF 4.3).

18.Mingli Han*, Manran Liu, Yimeng Wang, Xin Chen, Jianli Xu, Yan Sun, Liuyang Zhao, Hongbo Qu, Yuanming Fan, Chengyi Wu#. Antagonism of miR-21 reverses epithelial-mesenchymal transition and cancer stem cell phenotype through AKT/ERK1/2 inactivation by targeting PTEN. PLoS ONE 2012, 7(6):e39520. (IF 4.1).

19.Mingli Han*, Yimeng Wang*, Manran Liu, Xiaokai Bi, Junjie Bao, Ni Zeng, Zhikun Zhu, Zhiqiang Mo, Chengyi Wu# and Xin Chen#. MiR-21 regulates epithelial-mesenchymal transition phenotype and hypoxia-inducible factor-1α expression in third-sphere forming breast cancer stem cell-like cells. Cancer Sci 2012, 103(6):1058-64. (IF 3.4).

20.Mingli Han*, Manran Liu, Yimeng Wang, Zhiqiang Mo, Xiaokai Bi, Zhirong Liu, Yuanming Fan, Xin Chen#, Chengyi Wu#. Re-expression of miR-21 contributes to migration and invasion by inducing epithelial-mesenchymal transition consistent with cancer stem cell characteristics in MCF-7 cells. Mol Cell Biochem 2012, 363(1-2):427-36. (IF 2.8).

21.Wenwen Li*, Manran Liu, Sihan Lai, Can Xu, Fang Lu, Xiaoqiu Xiao, and Yixi Bao#. Immunomodulatory effects of polysaccharopeptide (PSP) in human PBMC through regulation of TRAF6/TLR immunosignal-transduction pathways. Immunopharmacology Immunotoxicology 2010, 32(4): 576-584.

2011年以前于美国以第1作者或合作者发表的论文

22.Janowski E, Jiao X, Katiyar S, Lisanti MP, Liu M, Pestell RG, Morad M#. c-Jun is required for TGF-β-mediated cellular migration via nuclear Ca²⁺signaling. Int J Biochem Cell Biol. 2011, 43(8):1104-13. (IF 4.8).

23.Liu M*, Sakamaki T, Casimiro MC, Willmarth NE, Quong AA, Ju X, Ojeifo J, Jiao X, Yeow WS, Katiyar S, Shirley LA, Joyce D, Lisanti MP, Albanese C, Pestell RG#. The canonical NF-kappaB pathway governs mammary tumorigenesis in transgenic mice and tumor stem cell expansion. Cancer Res 2010, 70(24):10464-73. (IF 8.2).

24.Jiao X, Katiyar S, Willmarth NE, Liu M, Ma X, Flomenberg N, Lisanti MP, Pestell RG#. c-Jun induces mammary epithelial cellular invasion and breast cancer stem cell expansion. J Biol Chem 2010, 285(11):8218-26. (IF 5.4).

25.Liu M*, Casimiro MC, Wang C, Shirley LA, Jiao X, Katiyar S, Ju X, Li Z, Yu Z, Zhou J, Johnson M, Fortina P, Hyslop T, Windle JJ, Pestell RG#. p21CIP1 attenuates Ras- and c-Myc-dependent breast tumor epithelial mesenchymal transition and cancer stem cell-like gene expression in vivo. Proc Natl Acad Sci USA 2009, 106(45):19035-9. (IF 9.7).

26.Bonuccelli G, Casimiro MC, Sotgia F, Wang C, Liu M, Katiyar S, Zhou J, Dew E, Capozza F, Daumer KM, Minetti C, Milliman JN, Alpy F, Rio MC, Tomasetto C, Mercier I, Flomenberg N, Frank PG, Pestell RG, Lisanti MP#. Caveolin-1 (P132L), a common breast cancer mutation, confers mammary cell invasiveness and defines a novel stem cell/metastasis-associated gene signature. Am J Pathol 2009, 174(5):1650-62. (IF 5.7).

27.Liu M*, Ju X, Willmarth NE, Casimiro MC, Ojeifo J, Sakamaki T, Katiyar S, Jiao X, Popov VM, Yu Z, Wu K, Joyce D, Wang C, Pestell RG#. Nuclear factor-kappaB enhances ErbB2-induced mammary tumorigenesis and neoangiogenesis in vivo. Am J Pathol 2009, 174(5):1910-20. (IF 5.7).

28.Sotgia F, Casimiro MC, Bonuccelli G, Liu M, Whitaker-Menezes D, Er O, Daumer KM, Mercier I, Witkiewicz AK, Minetti C, Capozza F, Gormley M, Quong AA, Rui H, Frank PG, Milliman JN, Knudsen ES, Zhou J, Wang C, Pestell RG, Lisanti MP#. Loss of caveolin-3 induces a lactogenic microenvironment that is protective against mammary tumor formation. Am J Pathol 2009, 174(2):613-29. (IF 5.7).

29.Lindsay J, Jiao X, Sakamaki T, Casimiro MC, Shirley LA, Tran TH, Ju X, Liu M, Li Z, Wang C, Katiyar S, Rao M, Allen KG, Glazer RI, Ge C, Stanley P, Lisanti MP, Rui H, Pestell RG#. ErbB2 induces Notch1 activity and function in breast cancer cells. Clin Transl Sci 2008, 1(2):107-15.

30.Yu Z, Wang C, Wang M, Li Z, Casimiro MC, Liu M, Wu K, Whittle J, Ju X, Hyslop T, McCue P, Pestell RG#. A cyclin D1/microRNA 17/20 regulatory feedback loop in control of breast cancer cell proliferation. J Cell Biol 2008, 182(3):509-17. (IF 10.2).

31.Wu K, Katiyar S, Li A, Liu M, Ju X, Popov VM, Jiao X, Lisanti MP, Casola A, Pestell RG#. Dachshund inhibits oncogene-induced breast cancer cellular migration and invasion through suppression of interleukin-8. Proc Natl Acad Sci USA 2008, 105(19):6924-9. (IF 9.8).

32.Rao M, Casimiro MC, Lisanti MP, D\'Amico M, Wang C, Shirley LA, Leader JE, Liu M, Stallcup M, Engel DA, Murphy DJ, Pestell RG#. Inhibition of cyclin D1 gene transcription by Brg-1. Cell Cycle 2008, 7(5):647-55. (IF 5.1).

33.Jiao X, Katiyar S, Liu M, Mueller SC, Lisanti MP, Li A, Pestell TG, Wu K, Ju X, Li Z, Wagner EF, Takeya T, Wang C, Pestell RG#. Disruption of c-Jun reduces cellular migration and invasion through inhibition of c-Src and hyperactivation of ROCK II kinase. Mol Biol Cell 2008, 19(4):1378-90. (IF 6.3).

34.Ju X, Katiyar S, Wang C, Liu M, Jiao X, Li S, Zhou J, Turner J, Lisanti MP, Russell RG, Mueller SC, Ojeifo J, Chen WS, Hay N, Pestell RG#. Akt1 governs breast cancer progression in vivo. Proc Natl Acad Sci USA 2007, 104(18):7438-43. (IF 9.8).

35.Wu K, Liu M, Li A, Donninger H, Rao M, Jiao X, Lisanti MP, Cvekl A, Birrer M, Pestell RG#. Cell fate determination factor DACH1 inhibits c-Jun-induced contact-independent growth. Mol Biol Cell 2007, 18(3):755-67. (IF 2.8). (IF 6.5).

36.Wu K, Li A, Rao M, Liu M, Dailey V, Yang Y, Di Vizio D, Wang C, Lisanti MP, Sauter G, Russell RG, Cvekl A, Pestell RG#. DACH1 is a cell fate determination factor that inhibits cyclin D1 and breast tumor growth. Mol Cell Biol 2006, 26(19):7116-29. (IF 6.7).

37.Fu M*, Liu M*, Sauve AA, Jiao X, Zhang X, Wu X, Powell MJ, Yang T, Gu W, Avantaggiati ML, Pattabiraman N, Pestell TG, Wang F, Quong AA, Wang C, Pestell RG#. Hormonal control of androgen receptor function through SIRT1. Mol Cell Biol 2006, 26(21):8122-35. (IF 6.7).

38.Sakamaki T, Casimiro MC, Ju X, Quong AA, Katiyar S, Liu M, Jiao X, Li A, Zhang X, Lu Y, Wang C, Byers S, Nicholson R, Link T, Shemluck M, Yang J, Fricke ST, Novikoff PM, Papanikolaou A, Arnold A, Albanese C, Pestell R#. Cyclin D1 determines mitochondrial function in vivo. Mol Cell Biol 2006, 26(14):5449-69. (IF 6.8).

39.Liu MR, Pan KF, Li ZF, Wang Y, Deng DJ, Zhang L, Lu YY#. Rapid screening mitochondrial DNA mutation by using denaturing high-performance liquid chromatography. World J Gastroenterol 2002, 8(3):426-30. (IF 2.4).