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癌细胞信号网络动力学研究

李翔 刘锋 帅建伟

癌细胞信号网络动力学研究

李翔, 刘锋, 帅建伟
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  • 癌症不仅是一种基因突变疾病,更是一种涉及诸如增殖、分化、凋亡和侵袭等多条细胞命运抉择的信号转导通路疾病. 癌细胞内的信号通路虽然非常复杂但我们可以专注于关键蛋白的信号网络建模,定量研究癌细胞核心信号通路的动力学和功能调控机理. 本文结合一些具体网络模型,介绍癌细胞信号网络动力学的研究进展. 首先介绍信号网络的基序动力学研究,然后讨论细胞存活、增殖、侵袭、凋亡等单个功能模块的网络建模,以及几个模块耦合的信号网络,和以癌细胞为整体的癌细胞信号网络建模. 这些研究表明,基于核心信号通路动力学的研究确实能促进对肿瘤发生发展机理的了解,为肿瘤的治疗和药物靶点的设计提供线索和思路,这些令人振奋的研究将激发未来更多类似的工作.
      通信作者: 帅建伟, jianweishuai@xmu.edu.cn
    • 基金项目: 国家重点基础研究发展计划(批准号:2013CB834104)、国家自然科学基金(批准号:31370830,11175084,31361163003)和福建省高校领军人才资助的课题.
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    Fischer K R, Durrans A, Lee S, Sheng J, Li F, Wong S T, Choi H, El Rayes T, Ryu S, Troeger J, Schwabe R F, Vahdat L T, Altorki N K, Mittal V, Gao D 2015 Nature 527 472

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  • [1]

    Torre L, Bray F, Siegle R L, Ferlay J, Lortet-Tieulent J, Jemal A 2012 CA Cancer J. Clin. 65 87

    [2]

    Chen W, Zheng R, Baade P D, Zhang S, Zeng H, Bray F, Jemal A, Yu X Q, He J 2015 CA Cancer J. Clin. 66 115

    [3]

    Hanahan D and Weinberg R A 2011 Cell 144 646

    [4]

    Hanahan D and Weinberg R A 2000 Cell 100 57

    [5]

    Futreal P A, Kasprzyk A, Birney E, Mullikin J C, Wooster R, Stratton M R 2001 Nature 409 850

    [6]

    Parsons D W, Jones S, Zhang X Lin J C, Leary R J, Angenendt P, Mankoo P, Carter H, Siu I M, Gallia G L, Olivi A, McLendon R, Rasheed B A, Keir S, Nikolskaya T, Nikolsky Y, Busam D A, Tekleab H, Diaz L A Jr, Hartigan J, Smith D R, Strausberg R L, Marie S K, Shinjo S M, Yan H, Riggins G J, Bigner D D, Karchin R, Papadopoulos N, Parmigiani G, Vogelstein B, Velculescu V E, Kinzler K W 2008 Science 321 1807

    [7]

    Jones S, Zhang X, Parsons D W, Lin J C, Leary R J, Angenendt P, Mankoo P, Carter H, Kamiyama H, Jimeno A, Hong S M, Fu B, Lin M T, Calhoun E S, Kamiyama M, Walter K, Nikolskaya T, Nikolsky Y, Hartigan J, Smith D R, Hidalgo M, Leach S D, Klein A P, Jaffee E M, Goggins M, Maitra A, Iacobuzio-Donahue C, Eshleman J R, Kern S E, Hruban R H, Karchin R, Papadopoulos N, Parmigiani G, Vogelstein B, Velculescu V E, Kinzler K W 2008 Science 321 1801

    [8]

    Cancer Genome Atlas Research Network 2008 Nature 455 1061

    [9]

    Citri A, Yarden Y 2006 Nat. Rev. Mol. Cell Biol. 7 505

    [10]

    Hood L 2003 Mech. Ageing Dev. 124 9

    [11]

    Kitano H 2002 Science 295 1662

    [12]

    Iyengar R 2009 Sci. Signal 2 eg3

    [13]

    Friedman N, Linial M, Nachman I, Pe'er D 2000 J. Comput. Biol. 7 601

    [14]

    Kauffman S 1969 Nature 224 177

    [15]

    Schoeberl B, Eichler-Jonsson C, Gilles E D, Mller G 2002 Nat. Biotechnol. 20 370

    [16]

    Markevich N I, Tsyganov M A, Hoek J B, Kholodenko B N 2006 Mol. Syst. Biol. 2 61

    [17]

    Gillespie D T 2007 Annu. Rev. Phys. Chem. 58 35

    [18]

    Kirkpatrick S, Vecchi M P 1983 Science 220 671

    [19]

    Holland J H 1975 Adaptation in natural and artificial systems: an introductory analysis with applications to biology, control, and artificial intelligence (Ann Arbor: Control Artificial Intelligence University of Michigan Press)

    [20]

    Jerne N K 1974 Ann. Immunol. (Paris) 125C 373

    [21]

    Kreeger P K, Lauffenburger D A 2010 Carcinogenesis 31 2

    [22]

    Khalil I G, Hill C 2005 Curr. Opin. Oncol. 17 44

    [23]

    Aldridge B B, Burke J M, Lauffenburger D A, Sorger P K 2006 Nat. Cell. Biol. 8 1195

    [24]

    Zhang X P, Cheng Z, Liu F, Wang W 2007 Phys. Rev. E 76 031924.

    [25]

    Tian X J, Zhang X P, Liu F, Wang W 2009 Phys. Rev. E 80 011926

    [26]

    Lu M, Jolly M K, Levine H, Onuchic J N, Ben-Jacob E 2013 Proc. Natl. Acad. Sci. USA. 110 18144

    [27]

    Huang B, Xia Y, Liu F, Wang W 2016 Sci. Rep. 6 28096

    [28]

    Karin M, Lin A 2002 Nat. Immunol. 3 221

    [29]

    Perkins N D 2012 Nat. Rev. Cancer 12 121

    [30]

    Nakanishi C, Toi M 2005 Nat. Rev. Cancer 5 297

    [31]

    Karin M, Ben-Neriah Y 2000 Annu. Rev.Immunol. 18 621

    [32]

    Hoffmann A, Levchenko A, Scott M L, Baltimore D 2002 Science 298 1241

    [33]

    Parada L F, Tabin C J, Shih C, Weinberg R A 1982 Nature 297 474

    [34]

    Bos J L 1989 Cancer Res. 49 4682

    [35]

    Bos J L, Rehmann H, Wittinghofer A 2007 Cell 129 865

    [36]

    Stites E C, Trampont P C, Ma Z, Ravichandran K S 2007 Science 318 463

    [37]

    Thiery J P 2002 Nat. Rev. Cancer 2 442

    [38]

    Nakaya Y, Sheng G 2008 Dev. Growth Differ. 50 755

    [39]

    Morel A P, Livre M, Thomas C, Hinkal G, Ansieau S, Puisieux A 2008 PLoS One 3 e2888

    [40]

    Yang A D, Camp E R, Fan F, Shen L, Gray M J, Liu W, Somcio R, Bauer T W, Wu Y, Hicklin D J, Ellis L M 2006 Cancer Res. 66 46

    [41]

    De Craene B, Berx G 2013 Nat. Rev. Cancer 13 97

    [42]

    Steinway S N, Zaudo J G, Ding W, Rountree C B, Feith D J, Loughran T P Jr, Albert R 2014 Cancer Res. 74 5963

    [43]

    Tait S W, Green D R 2010 Nat. Rev. Mol. Cell Biol. 11 621

    [44]

    Zhao L, Sun T, Pei J, Ouyang Q 2015 Proc. Natl. Acad. Sci. USA. 112 E4046

    [45]

    Zhang X P, Liu F, Cheng Z, Wang W 2009 Proc. Natl. Acad. Sci. USA. 106 12245

    [46]

    Zhang X P, Liu F, Wang W 2011 Proc. Natl. Acad. Sci. USA. 108 8990

    [47]

    Beg A A, Sha W C, Bronson R T, Ghosh S, Baltimore D 1995 Nature 376 167

    [48]

    Neumann L, Pforr C, Beaudouin J, Pappa A, Fricker N, Krammer P H, Lavrik I N, Eils R 2010 Mol. Syst. Biol. 6 352

    [49]

    Takahashi R, Deveraux Q, Tamm I, Welsh K, Assa-Munt N, Salvesen G S, Reed J C 1998 J. Biol. Chem. 273 7787

    [50]

    Khoshnan A, Tindell C, Laux I, Bae D, Bennett B, Nel A E 2000 J. Immunol. 165 1743

    [51]

    Li X, Chen Y, Qi H, Liu L, Shuai J 2016 Oncotarget 7 34599

    [52]

    Futreal P A, Coin L, Marshall M, Down T, Hubbard T, Wooster R, Rahman N, Stratton M R 2004 Nat. Rev. Cancer 4 177

    [53]

    Kitano H 2004 Nat. Rev. Cancer. 4 227

    [54]

    Pujana M A, Han J D, Starita L M, Stevens K N, Tewari M, Ahn J S, Rennert G, Moreno V, Kirchhoff T, Gold B, Assmann V, Elshamy W M, Rual J F, Levine D, Rozek L S, Gelman R S, Gunsalus K C, Greenberg R A, Sobhian B, Bertin N, Venkatesan K, Ayivi-Guedehoussou N, Sol X, Hernndez P, Lzaro C, Nathanson K L, Weber B L, Cusick M E, Hill D E, Offit K, Livingston D M, Gruber S B, Parvin J D, Vidal M 2007 Nat. Genet. 39 1338

    [55]

    Lei X, Tian W, Zhu H, Chen T, Ao P 2015 Scientific Reports 5 13597

    [56]

    Barros R, Freund J N, David L, Almeida R 2012 Trends Mol. Med. 18 555

    [57]

    Tsukamoto T, Inada K, Tanaka H, Mizoshita T, Mihara M, Ushijima T, Yamamura Y, Nakamura S, Tatematsu M 2004 J. Cancer Res. Clin. Oncol. 130 135

    [58]

    Li S, Zhu X, Liu B, Wang G, Ao P 2015 Oncotarget 6 13607

    [59]

    Anderson A R, Quaranta V 2008 Nat. Rev. Cancer 8 227

    [60]

    Tomasetti C, Vogelstein B 2015 Science 347 78

    [61]

    Stratton M R, Campbell P J, Futreal P A 2009 Nature 458 719

    [62]

    Fischer K R, Durrans A, Lee S, Sheng J, Li F, Wong S T, Choi H, El Rayes T, Ryu S, Troeger J, Schwabe R F, Vahdat L T, Altorki N K, Mittal V, Gao D 2015 Nature 527 472

    [63]

    Li W, Kang Y 2016 Trends Cancer 2 65

    [64]

    Wei S C, Yang J 2016 Trends Cell Biol. 26 111

    [65]

    Bild A H, Potti A, Nevins J R 2006 Nat. Rev. Cancer 6 735

    [66]

    Wang Z, Deisboeck T S 2014 Drug Discov. Today 19 145

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出版历程
  • 收稿日期:  2016-06-06
  • 修回日期:  2016-06-27
  • 刊出日期:  2016-09-05

癌细胞信号网络动力学研究

  • 1. 厦门大学物理系, 厦门 361005;
  • 2. 南京大学物理系, 南京 210093
  • 通信作者: 帅建伟, jianweishuai@xmu.edu.cn
    基金项目: 

    国家重点基础研究发展计划(批准号:2013CB834104)、国家自然科学基金(批准号:31370830,11175084,31361163003)和福建省高校领军人才资助的课题.

摘要: 癌症不仅是一种基因突变疾病,更是一种涉及诸如增殖、分化、凋亡和侵袭等多条细胞命运抉择的信号转导通路疾病. 癌细胞内的信号通路虽然非常复杂但我们可以专注于关键蛋白的信号网络建模,定量研究癌细胞核心信号通路的动力学和功能调控机理. 本文结合一些具体网络模型,介绍癌细胞信号网络动力学的研究进展. 首先介绍信号网络的基序动力学研究,然后讨论细胞存活、增殖、侵袭、凋亡等单个功能模块的网络建模,以及几个模块耦合的信号网络,和以癌细胞为整体的癌细胞信号网络建模. 这些研究表明,基于核心信号通路动力学的研究确实能促进对肿瘤发生发展机理的了解,为肿瘤的治疗和药物靶点的设计提供线索和思路,这些令人振奋的研究将激发未来更多类似的工作.

English Abstract

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