分子腫瘤學(xué)研究室是專注于食管癌、胃癌的基因組學(xué)、分子生物學(xué)和臨床轉(zhuǎn)化的開放型研究科室。研究室主任由中國工程院詹啟敏院士擔(dān)任，研究室對國內(nèi)外實(shí)行開放，并與美國國家癌癥研究所(NCI)、M.D.
Anderson癌癥中心、美國匹茲堡大學(xué)醫(yī)學(xué)院腫瘤研究所、英國ICRF、世界衛(wèi)生組織(WHO)進(jìn)行多項(xiàng)合作研究和學(xué)術(shù)交流。
團(tuán)隊(duì)研究方向
一.主要針對我國特發(fā)、高發(fā)的消化道腫瘤(食管癌和胃癌)運(yùn)用基因組學(xué)、分子生物學(xué)和模式動物開展系統(tǒng)研究;
二.利用生物信息學(xué)分析對大規(guī)模基因組測序數(shù)據(jù)進(jìn)行深度挖掘，尋找與臨床診斷、干預(yù)、治療相關(guān)的分子標(biāo)志物和藥物靶點(diǎn)，預(yù)后判斷分子靶標(biāo);
三.對食管癌、胃癌發(fā)生發(fā)展的分子生物學(xué)機(jī)制開展深層次研究，主要切入點(diǎn)為細(xì)胞周期調(diào)控、腫瘤代謝和信號傳導(dǎo);
四.重點(diǎn)關(guān)注基因組改變(包括基因突變/拷貝數(shù)改變/Indel/染色體結(jié)構(gòu)變異等)、非編碼RNA(LncRNA/miRNA)、蛋白質(zhì)、外泌體與臨床腫瘤發(fā)展、治療敏感性以及臨床轉(zhuǎn)歸之相關(guān)性。
團(tuán)隊(duì)近年研究成果
食管鱗癌基因組學(xué)變異研究
通過應(yīng)用高通量測序和比較基因組雜交芯片技術(shù)，利用基因組學(xué)、生物信息學(xué)、分子生物學(xué)、臨床病理學(xué)理論和技術(shù)完成了人類食管鱗癌基因組變異的分析，詹啟敏院士團(tuán)隊(duì)發(fā)現(xiàn)158例食管鱗癌組織中存在8個(gè)明顯的基因變異，包括7個(gè)已知的腫瘤相關(guān)基因(TP53、RB1、CDKN2A、PIK3CA、NOTCH1、NFE2L2、ADAM29)、1個(gè)以前從未報(bào)道過的腫瘤基因FAM135B，進(jìn)一步研究發(fā)現(xiàn)，F(xiàn)AM135B是一種能夠增加食管鱗癌細(xì)胞惡性程度的促癌基因。同時(shí)通過獲得的食管鱗癌拷貝數(shù)變異的重要數(shù)據(jù)，發(fā)現(xiàn)位于染色體11q13.3-13.4擴(kuò)增區(qū)域的MIR548K參與食管鱗癌惡性表型的形成。此外，研究還揭示了組蛋白調(diào)節(jié)基因突變(MLL2、ASHL1L、MLL3、SETD1B、CREBBP/EP300);發(fā)現(xiàn)PI3K等潛在藥靶;確定了Wnt、Cell
cycle、Akt、Notch、RTK-Ras等食管癌發(fā)生發(fā)展相關(guān)重要通路等，此項(xiàng)研究首次全面系統(tǒng)揭示了食管鱗癌的遺傳突變背景，發(fā)現(xiàn)了食管鱗癌重要的突變基因及通路，對深入研究食管鱗癌的發(fā)生發(fā)展機(jī)制具有指導(dǎo)意義，亦為藥物研發(fā)及個(gè)性化治療方法提供了科學(xué)依據(jù)。
研究成果于2014年在線發(fā)表于國際學(xué)術(shù)權(quán)威雜志《Nature》(影響因子38.1)。
非編碼RNA的生物學(xué)功能和分子機(jī)制研究
詹啟敏院士團(tuán)隊(duì)發(fā)現(xiàn)，長鏈非編碼RNA
gadd7調(diào)控細(xì)胞周期進(jìn)程，并參與UV誘導(dǎo)的細(xì)胞G1/S檢驗(yàn)點(diǎn)調(diào)控過程。機(jī)制研究顯示，gadd7特異性結(jié)合于TDP-43蛋白，有效抑制TDP-43 與CDK6
mRNA 的結(jié)合，從而導(dǎo)致CDK6 mRNA 降解。這一發(fā)現(xiàn)進(jìn)一步豐富了人們對長鏈非編碼RNA功能和機(jī)制多樣性的認(rèn)識。
研究成果于2012年發(fā)表于國際高水平雜志《EMBO J》(影響因子9.822)，并得到F1000推薦，被cell等頂級刊物引用。
GADD45A抑制腫瘤細(xì)胞的自噬的分子機(jī)制
詹啟敏院士團(tuán)隊(duì)發(fā)現(xiàn)GADD45A可以抑制腫瘤細(xì)胞的自噬過程，進(jìn)一步機(jī)制研究發(fā)現(xiàn)GADD45A可以與BECN1相互作用，從而破壞了BECN1/PIK3C3復(fù)合物。這一發(fā)現(xiàn)為腫瘤的治療，尤其是放化療后防止腫瘤復(fù)發(fā)提供了有用的靶點(diǎn)。
該成果于2015年發(fā)表于《Autophagy》(影響因子9.108)。
食管癌惡性進(jìn)展的分子生物學(xué)機(jī)制研究
詹啟敏院士團(tuán)隊(duì)發(fā)現(xiàn)血小板活化因子受體(Platelet-activating factor receptor, PAFR)與食管鱗癌
(esophageal squamous cell carcinoma,
ESCC)惡性進(jìn)展密切相關(guān)。機(jī)制研究顯示，PAFR能夠與黏著斑激酶(FAK)結(jié)合，誘導(dǎo)其激活PI3K/Akt/NF-κB信號通路，進(jìn)而調(diào)控下游多種促癌基因的表達(dá)，促進(jìn)食管鱗癌的惡性增殖，侵襲及誘導(dǎo)內(nèi)皮細(xì)胞血管新生的能力，詳細(xì)闡明了PAFR誘導(dǎo)食管鱗癌惡性進(jìn)展的分子機(jī)制。此外，本研究亦通過使用具有成藥性的膽固醇包被的PAFR
siRNA抑制小鼠荷瘤模型中食管鱗癌的惡性進(jìn)展及促癌基因的表達(dá)，進(jìn)一步為開發(fā)以PAFR為靶點(diǎn)的信號通路抑制劑提供了堅(jiān)實(shí)的理論依據(jù)。
相關(guān)研究成果于2015年發(fā)表在國際腫瘤學(xué)著名期刊《Oncogene》上(影響因子：8.59)。
非小細(xì)胞肺癌惡性進(jìn)展的分子生物學(xué)機(jī)制研究
詹啟敏院士團(tuán)隊(duì)發(fā)現(xiàn)在非小細(xì)胞肺癌的研究中發(fā)現(xiàn)PAF/PAFR信號軸能夠通過激活小G蛋白，誘導(dǎo)JAK2/Src/STAT3信號通路的活性，而激活的STAT3能夠轉(zhuǎn)錄性激活PAFR表達(dá)并形成正反饋環(huán)，進(jìn)而介導(dǎo)PAFR調(diào)控的非小細(xì)胞肺癌上皮-間質(zhì)轉(zhuǎn)化(Epithelial-mesenchymal
transition ,EMT)及侵襲轉(zhuǎn)移，為開發(fā)腫瘤治療提供了新的機(jī)制研究的思路和靶點(diǎn)。相關(guān)研究成果于2015年發(fā)表于國際腫瘤學(xué)著名期刊《Cancer
Research》上(影響因子：9.329)。
近五年代表性論文
1. Cheng C, Zhou Y, Li H, Xiong T, Li S, Bi Y, Kong P, Wang F, Cui H, Li Y,
Fang X, Yan T, Li Y, Wang J, Yang B, Zhang L, Jia Z, Song B, Hu X, Yang J, Qiu
H, Zhang G, Liu J, Xu E, Shi R, Zhang Y, Liu H, He C, Zhao Z, Qian Y, Rong R,
Han Z, Zhang Y, Luo W, Wang J, Peng S, Yang X, Li X, Li L, Fang H, Liu X, Ma L,
Chen Y, Guo S, Chen X, Xi Y, Li G, Liang J, Yang X, Guo J, Jia J, Li Q, Cheng X,
Zhan Q*, Cui Y* (2016) Whole-Genome Sequencing Reveals Diverse Models of
Structural Variations in Esophageal Squamous Cell Carcinoma. Am J Hum
Genet98(2):256-74.
2. Dongdong Zhang, Weimin Zhang, Dan Li, Ming Fu, Runsheng Chen , andQimin
Zhan*. GADD45A Inhibits autophagy by regulating the Interaction between BECN1
and PIK3C3. Autophagy.2015,11 (12): 2247-2258.
3. Ling Zhang, Yong Zhou, Caixia Cheng, Heyang Cui, Le Cheng, Pengzhou Kong,
Jiaqian Wang, Yin Li, Wenliang Chen, Bin Song, Fang Wang, Zhiwu Jia, Lin Li,
Yaoping Li, Bin Yang, Jing Liu, Ruyi Shi, Yanghui Bi, Yanyan Zhang, Juan Wang,
Zhenxiang Zhao, Xiaoling Hu, Jie Yang, Hongyi Li, Zhibo Gao, Gang Chen, Xuanlin
Huang, Xukui Yang, Shengqing Wan, Chao Chen, Bin Li, Yongkai Tan, Longyun Chen,
Minghui He, Sha Xie, Xiangchun Li, Xuehan Zhuang, Mengyao Wang, Zhi Xia, Longhai
Luo, Jie Ma, Bing Dong, Jiuzhou Zhao, Yongmei Song, Yunwei Ou, Enming Li, Liyan
Xu, Jinfen Wang, Yanfeng Xi, Guodong Li, Enwei Xu, Jianfang Liang, Xiaofeng
Yang, Jiansheng Guo, Xing Chen, Yanbo Zhang, Qingshan Li, Lixin Liu, Yingrui Li,
Xiuqing Zhang, Huanming Yang, Dongxin Lin, Xiaolong Cheng, Yongjun Guo, Jun
Wang,Qimin Zhan*, and Yongping Cui*. Genomic Analyses Reveal Mutational
Signatures and Frequently Altered Genes in Esophageal SquamousCell Carcinoma. Am
J Hum Genet. 2015, 96(4):597-611.
4. Jie Chen, Tian Lan,Weimin Zhang, Lijia Dong, Nan Kang, Shumin Zhang,Ming
Fu, Bing Liu, Kangtai Liu, andQimin Zhan*.Feed-Forward Reciprocal Activation of
PAFR and STAT3 Regulates Epithelial-Mesenchymal Transition in Non-Small Cell
Lung Cancer. Cancer Res.2015,75(19):4198-4210.
5. J Chen,T Lan,W Zhang,L Dong,N Kang,S Zhang,M Fu,B Liu,K Liu,C Zhang,J Hou
and Q Zhan*.Platelet-activating factor receptor-mediated PI3K/AKT activation
contributes to the malignant development of esophageal squamous cell
carcinoma.Oncogene. 2015,34(40):5114-5127.
6. Li D, Kang N, Ji J, Zhan Q (2015) BRCA1 regulates transforming growth
factor-β (TGF-β1) signaling through Gadd45a by enhancing the protein stability
of Smad4. Mol Oncol 9(8):1655-66.
7. Jian Liu, Haijuan Wang, Fei Ma, Dongkui Xu, Yanan Chang, Jinlong Zhang,
Jia Wang, Mei Zhao, Chen Lin, Changzhi Huang*, Haili Qian*,Qimin Zhan*. MTA1
regulates higher-order chromatin structure and histone H1-chromatin. Mol Oncol.
2015. 9(1): 218-235.
8. Dong Y, Zhao Q, Ma X, Ma G, Liu C, Chen Z, Yu L, Liu X, Zhang Y, Shao S,
Xiao J, Li J, Zhang W, Fu M, Dong L, Yang X, Guo X, Xue L, Fang F, Zhan Q*,
Zhang L*. (2015) Establishment of a new OSCC cell line derived from OLK and
identification of malignant transformation-related proteins by differential
proteomics approach. Sci Rep 5:12668.
9. Yongmei Song,Lin Li,Yunwei Ou,Zhibo Gao,Enmin Li,Xiangchun Li,Weimin
Zhang, Jiaqian Wang,Liyan Xu,Yong Zhou,Xiaojuan Ma,Lingyan Liu,Zitong
Zhao,Xuanlin Huang,Jing Fan,Lijia Dong,Gang Chen,Liying Ma,Jia Yang,Longyun
Chen,Minghui He,Miao Li,Xuehan Zhuang,Kai Huang,Kunlong Qiu,Guangliang
Yin,Guangwu Guo,Qiang Feng,Peishan Chen,Zhiyong Wu,Jianyi Wu,Ling Ma,Jinyang
Zhao,Longhai Luo,Ming Fu,Bainan Xu,Bo Chen,Yingrui Li,Tong Tong,Mingrong
Wang,Zhihua Liu,Dongxin Lin,Xiuqing Zhang,Huanming Yang,Jun Wang & Qimin
Zhan*.Identification of genomic alterations in oesophageal squamous cell cancer.
Nature.2014, 509 (7498):91-95.
10. Yue Zhao, Wei Zhou, Liyan Xue, Weimin Zhang,Qimin Zhan*.Nicotine
Activates YAP1 through nAChRs Mediated Signaling in Esophageal Squamous Cell
Cancer (ESCC). PLoS One.2014,9(3):e90836.
11. Xiao Li, Jing Suo, Shujuan Shao, Liyan Xue, Wei Chen, Lijia Dong, Ji Shi,
Ming Fu, Ning Lu,Qimin Zhan*, Tong Tong*.Overexpression of OLC1 Promotes
Tumorigenesis of Human Esophageal Squamous Cell Carcinoma. PLoS
One.2014,9(3):e90958.2232-2239.
12. Jianzhong Cao, Yongmei Song, Nan Bi, Jie Shen, Wenyang Liu, Jing Fan,
Guogui Sun, Tong Tong, Jie He, Yuankai Shi, Xun Zhang, Ning Lu, Yinghua He,
Hongyu Zhang, KelongMa, Xiaoying Luo, Lei Lv, Hui Deng, Jing Cheng, Jingde Zhu,
Luhua Wang, andQimin Zhan*.DNA Methylation-Mediated Repression of miR-886-3p
Predicts Poor Outcome of Human Small Cell Lung Cancer. Cancer Res.
2013,73(11):3326-3335.
13. Fang Yang, Weimin Zhang, Dan Li, andQimin Zhan*.Gadd45a Suppresses Tumor
Angiogenesis via Inhibition of the mTOR/STAT3 Protein Pathway. J. Biol. Chem.
2013,288(9):6552-6560.
14. Yunwei Ou, Liying Ma, Ling Ma, Zhen Huang, Wei Zhou, Chunling Zhao,
Bailin Zhang, Yongmei Song*, Chunjiang Yu*, andQimin Zhan*. Overexpression of
cyclin B1 antagonizes chemotherapeutic-induced apoptosis through PTEN/Akt
pathway in human esophageal squamous cell carcinoma cells. Cancer Biology &
Therapy. 2013,14(1):45-55.
15. Xuefeng Liu,Dan Li,Weimin Zhang,Mingzhou Guo and Qimin Zhan*. Long
non-coding RNA gadd7 interacts with TDP-43 and regulates Cdk6 mRNA decay.EMBO
JOURNAL.2012,31(23):4415-4427.
16. Yunwei Ou,Ling Ma,Lijia Dong,Liying Ma,Zitong Zhao,Li Ma,Wei Zhou,Jing
Fan,Chuanyue Wu,Chunjiang Yu*,Qimin Zhan*, and Yongmei Song*.Migfilin Protein
Promotes Migration and Invasion in Human Glioma through Epidermal Growth Factor
Receptor-mediated Phospholipase C-γ and STAT3 Protein Signaling Pathways. J.
Biol. Chem.2012,287(39): 32394–32405.
17. Yulin Chen,Dan Li,Dapeng Wang,Xuefeng Liu,Ning Yin,Yongmei Song,Shih Hsin
Lu,Zhenyu Ju, andQimin Zhan*. Quiescence and Attenuated DNA Damage Response
Promote Surivival of Esophageal Cancer Stem Cells. J Cell
Biol.2012,12:3643-3652.
18. Xuefeng Liu,Xiaomei Zhang,Qimin Zhan,Malcolm V. Brock,James G. Herman*
and Mingzhou Guo*. CDX2 serves as a Wnt signaling inhibitor and is frequently
methylated in lung cancer.Cancer Biol Ther. 2012,13(12):1152-1157.
19. Lihui Zou, Yimin Sun, Mingrong Wang,Qimin Zhan *. Aurora-A Interacts with
AP-2α and Down Regulates Its Transcription Activity. PLOS ONE. 2011,
6(8):e23110.
20. J Li and Q Zhan *.The role of centrosomal Nlp in the control of mitotic
progression and tumourigenesis. BRITISH JOURNAL OF CANCER. 2011, 104 (10):
1523-1528.
近五年授權(quán)發(fā)明專利：
1. HULC siRNA及其在制備治療肝癌的藥物中的用途. ZL201010512412.5. 詹啟敏;李丹;宋詠梅;童彤;劉雪峰;付明.
2. USE OF TWO MICRORNA MOLECULARS IN LUNG CANCER PROGNOSIS AND MEDICINE
PREPARATION. US 8,664,191,B2.Qimin Zhan;Lühua Wang;Nan Bi;Yongmei Song;Jianzhong
Cao;Wenyang Liu.
3. USE OF TWO MICRORNA MOLECULARS IN LUNG CANCER PROGNOSIS AND MEDICINE
PREPARATION. EP 2 462 951 B1. Qimin Zhan;Lühua Wang;Nan Bi;Yongmei
Song;Jianzhong Cao;Wenyang Liu.
4. 兩個(gè)microRNA分子在肺癌預(yù)后及藥物制備中的用途. 日本第5546064號. 詹啟敏;王綠化;畢楠;宋詠梅;曹建忠;劉文揚(yáng).
5. 兩個(gè)microRNA分子在肺癌預(yù)后及藥物制備中的用途. ZL200980158671.8. 詹啟敏;王綠化;畢楠;宋詠梅;曹建忠;劉文揚(yáng).
申請發(fā)明專利：
1. FAM135B抑制劑在治療和/或預(yù)防食管鱗狀細(xì)胞癌中的用途. 201410068807.9.詹啟敏，歐云尉，宋詠梅.
2. microRNA-548k抑制劑在治療和/或預(yù)防食管鱗狀細(xì)胞癌中的用途. 201410068887.8.詹啟敏，李林，宋詠梅.
3. 一種microRNA分子用于檢測和治療乳腺癌的用途. 201510813090.0. 詹啟敏;宋詠梅;趙梓彤;付明.
獲獎
1. 華夏醫(yī)學(xué)科技獎一等獎. 細(xì)胞周期破壞在惡性腫瘤發(fā)生發(fā)展中的作用.
中國醫(yī)學(xué)科學(xué)院腫瘤醫(yī)院-詹啟敏,宋詠梅,童彤,姬峻芳,高華,汪洋,付明,董立佳.
2. 中國抗癌協(xié)會科技獎一等獎. 細(xì)胞周期調(diào)控異常在腫瘤發(fā)生發(fā)展中的作用和分子機(jī)制研究.
中國醫(yī)學(xué)科學(xué)院腫瘤醫(yī)院-詹啟敏,宋詠梅,童彤,付明,劉雪鋒,歐云尉,邵淑娟,李丹,董立佳,王綠化.
承擔(dān)課題：
1. 腫瘤侵襲和轉(zhuǎn)移的惡性生物行為及分子干預(yù)(2009CB521800).973計(jì)劃.
2009.01-2013.12.首席科學(xué)家.
2. 惡性腫瘤癌前病變發(fā)生發(fā)展的分子機(jī)理研究(2015CB553900). 973計(jì)劃.
2015.01-2019.12.首席科學(xué)家.
3. 食管癌發(fā)生發(fā)展的分子機(jī)理研究(81021061).國家自然科學(xué)基金創(chuàng)新群體.
2011.01-2013.12.項(xiàng)目負(fù)責(zé)人.
4. 食管癌發(fā)生發(fā)展的分子機(jī)理研究(81321091).國家自然科學(xué)基金創(chuàng)新群體.
2014.01-2016.12.項(xiàng)目負(fù)責(zé)人.
5. 中心體蛋白BACP在腫瘤發(fā)生中的作用機(jī)制研究(30730046).
國家自然科學(xué)基金重點(diǎn)項(xiàng)目.2008.01-2011.12.項(xiàng)目負(fù)責(zé)人.
6. 細(xì)胞周期蛋白NlP在維持基因組穩(wěn)定和腫瘤發(fā)生中的作用和分子機(jī)制(81230047).
國家自然科學(xué)基金重點(diǎn)項(xiàng)目.2013.01-2017.12.項(xiàng)目負(fù)責(zé)人.
7. 腫瘤轉(zhuǎn)移相關(guān)lncRNA系統(tǒng)識別和功能研究(81490753).
國家自然科學(xué)基金重大項(xiàng)目.2015.01-2019.12.項(xiàng)目負(fù)責(zé)人.
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