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Application of physics in the study of cell polarity during tumor cell migration

Wang Jing Yang Gen Liu Feng

Application of physics in the study of cell polarity during tumor cell migration

Wang Jing, Yang Gen, Liu Feng
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  • Investigation of tumors from a physics perspective has attracted more and more attention since the initiation, development, and metastasis of tumors are strongly influenced by the physical interactions between the tumor cells and their microenvironments. Since tumor metastasis accounts for more than 90% of cancer-associated death, one of the focuses is to understand its underlying mechanism, especially how tumor cells polarize during their migration. Cell polarization directs tumor-cell migration in response to a spatial stimulus, e.g., the gradient of chemokine or oxygen molecules. It forms the front and back edges of cells by estiblishing asymmetric distributions of cell polarity proteins such as the Rho family GTPases and organelles such as Golgi. This paper reviews how the experimental and theoretical studies combining physics with biology reveal the underlying mechanisms of cell migration and cell polarity. Experimental results demonstrate that the physics clues including extracellular matrix's mechanical properties, dimensionality, and topography are strongly coupled with the biochemical reactions to establish and maintain the cell polarity and direct cell migration. The cell migration mode in a more physiological three-dimensional (3D) matrix is different from that in a two-dimensional(2D) system. Moreover, the membrane tension is suggested to maitain cell polarity by inhibiting polarization processes outside the front edge. On the other hand, a series of reaction diffusion models have been developed to characterize cell polarity. Representative examples inculding Turing-type model, local-excitation and global-inhibition (LEGI) model, and wave-pinning model can capture certain features of cell polarization, however none of them takes the physical factors, such as the membrane tension, into account hence fails to explain previous published experimental results about the membrane tension with cell polarization. To further improve our understanding of the mechanism of cell polarity, in the future study it is experimentally important to estiblish 3D tumor systems and study the gene regulation network that can control cell polariztion by advanced microscope; theroetically it is of importance to build mathematical models for the chemical reaction diffusion systems coupled with the mechanical factors such as membarne tension. These studies will reveal the molecular mechanism of cell polarization and cell migration under a more physiological relevant condition. They may also help us understand how the higher deformation ability of cancer stem cells provides the higher migration capability compared with the normal cancer cells. Ultimately, they will facilitate developing new therapeutic strategy against tumor metastasis by targeting the signaling of tumor cells in response of physical stimuli.
    • Funds: Project supported by the National Natural Science Foundation of China (Grant No. 11434001), and the Deparment of Science of China (Grant No. 2012YQ030142).
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    Gao L, Shao L, Chen B C, Betzig E 2014 Nat. Protoc. 9 1083

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    Mahou P, Vermot J, Beaurepaire E, Supatto W 2014 Nat. Methods. 11 600

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    Hanahan D, Weinberg R A 2011 Cell 144 646

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    Kreso A, Dick J E 2014 Cell. Stem. Cell. 14 275

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    Yang G, Quan Y, Wang W, Fu Q, Wu J, Mei T, Li J, Tang Y, Luo C, Ouyang Q, Chen S, Wu L, Hei T K, Wang Y 2012 Br. J. Cancer. 106 1512

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    Gupta P B, Fillmore C M, Jiang G, Shapira S D, Tao K, Kuperwasser C, Lander E S 2011 Cell 146 633

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  • [1]

    Weigelt B, Peterse J L, van't Veer L J 2005 Nat. Rev. Cancer. 5 591

    [2]

    Chaffer C L, Weinberg R A 2011 Science 331 1559

    [3]

    Wirtz D, Konstantopoulos K, Searson P C 2011 Nat. Rev. Cancer. 11 512

    [4]

    Lo C M, Wang H B, Dembo M, Wang Y L 2000 Biophys. J. 79 144

    [5]

    Bryan A K, Goranov A, Amon A, Manalis S R 2010 Proc. Natl. Acad. Sci. U. S. A. 107 999

    [6]

    Byun S, Son S, Amodei D, Cermak N, Shaw J, Kang J H, Hecht V C, Winslow M M, Jacks T, Mallick P, Manalis S R 2013 Proc. Natl. Acad. Sci. U. S. A. 110 7580

    [7]

    Guck J, Schinkinger S, Lincoln B, Wottawah F, Ebert S, Romeyke M, Lenz D, Erickson HM, Ananthakrishnan R, Mitchell D, Kas J, Ulvick S, Bilby C 2005 Biophys. J. 88 3689

    [8]

    Agus D B, Alexander J F, Arap W, Ashili S, Aslan J E, Austin R H, Backman V, Bethel K J, Bonneau R, Chen W C, Chen-Tanyolac C, Choi N C, Curley S A, Dallas M, Damania D, Davies P C, Decuzzi P, Dickinson L, Estevez-Salmeron L, Estrella V, Ferrari M, Fischbach C, Foo J, Fraley S I, Frantz C, Fuhrmann A, Gascard P, Gatenby R A, Geng Y, Gerecht S, Gillies R J, Godin B, Grady W M, Greenfield A, Hemphill C, Hempstead B L, Hielscher A, Hillis W D, Holland E C, Ibrahim-Hashim A, Jacks T, Johnson R H, Joo A, Katz J E, Kelbauskas L, Kesselman C, King M R, Konstantopoulos K, Kraning-Rush C M, Kuhn P, Kung K, Kwee B, Lakins J N, Lambert G, Liao D, Licht J D, Liphardt J T, Liu L, Lloyd M C, Lyubimova A, Mallick P, Marko J, McCarty O J, Meldrum D R, Michor F, Mumenthaler SM, Nandakumar V, O'Halloran TV, Oh S, Pasqualini R, Paszek M J, Philips K G, Poultney C S, Rana K, Reinhart-King C A, Ros R, Semenza G L, Senechal P, Shuler M L, Srinivasan S, Staunton J R, Stypula Y, Subramanian H, Tlsty T D, Tormoen G W, Tseng Y, van Oudenaarden A, Verbridge S S, Wan J C, Weaver V M, Widom J, Will C, Wirtz D, Wojtkowiak J, Wu P H 2013 Sci. Rep. 3 1449

    [9]

    Indra I, Undyala V, Kandow C, Thirumurthi U, Dembo M, Beningo K A 2011 Phys. Biol. 8 015015

    [10]

    Nagrath S, Sequist L V, Maheswaran S, Bell D W, Irimia D, Ulkus L, Smith M R, Kwak E L, Digumarthy S, Muzikansky A, Ryan P, Balis U J, Tompkins R G, Haber D A, Toner M 2007 Nature 450 1235

    [11]

    Ozkumur E, Shah A M, Ciciliano J C, Emmink B L, Miyamoto D T, Brachtel E, Yu M, Chen P I, Morgan B, Trautwein J, Kimura A, Sengupta S, Stott S L, Karabacak N M, Barber T A, Walsh J R, Smith K, Spuhler P S, Sullivan J P, Lee R J, Ting D T, Luo X, Shaw A T, Bardia A, Sequist L V, Louis D N, Maheswaran S, Kapur R, Haber D A, Toner M 2013 Sci. Transl. Med. 5 179ra47

    [12]

    Stott S L, Hsu C H, Tsukrov D I, Yu M, Miyamoto D T, Waltman B A, Rothenberg S M, Shah A M, Smas M E, Korir G K, Floyd F P Jr, Gilman A J, Lord J B, Winokur D, Springer S, Irimia D, Nagrath S, Sequist LV, Lee RJ, Isselbacher K J, Maheswaran S, Haber D A, Toner M 2010 Proc. Natl. Acad. Sci. U. S. A. 107 18392

    [13]

    Liu L, Sun B, Pedersen J N, Yong K-M A, Getzenberg R H, Stone H A, Austin R H 2011 Proc. Natl. Acad. Sci. U. S. A. 108 6853

    [14]

    Friedl P, Alexander S 2011 Cell 147 992

    [15]

    Tsai JH, Yang J 2013 Genes. Dev. 27 2192

    [16]

    Zhang J, Tian X J, Zhang H, Teng Y, Li R, Bai F, Elankumaran S, Xing J 2014 Sci. Signal. 7 ra91

    [17]

    Lu M, Jolly M K, Onuchic J, Ben-Jacob E 2014 Cancer. Res. 74 4574

    [18]

    Wolf K, Alexander S, Schacht V, Coussens LM, Andrian von UH, van Rheenen J, Deryugina E, Friedl P 2009 Semin. Cell. Dev. Biol. 20 931

    [19]

    Stroka K M, Konstantopoulos K 2014 Am. J. Physiol. Cell. Physiol. 306 C98

    [20]

    Gilmore A P, Burridge K 1996 Nature 381 531

    [21]

    Miyamoto S, Teramoto H, Coso O A, Gutkind J S, Burbelo P D, Akiyama S K, Yamada K M 1995 J. Cell. Biol. 131 791

    [22]

    Cukierman E, Pankov R, Stevens DR, Yamada KM 2001 Science 294 1708

    [23]

    Cukierman E, Pankov R, Yamada K M 2002 Curr. Opin. Cell. Biol. 14 633

    [24]

    Fraley S I, Feng Y, Krishnamurthy R, Kim D H, Celedon A, Longmore G D, Wirtz D 2010 Nat. Cell. Biol. 12 598

    [25]

    Petroll W M, Ma L, Jester J V 2003 J. Cell. Sci. 116 1481

    [26]

    Fraley S I, Feng Y, Giri A, Longmore G D, Wirtz D 2012 Nat. Commun. 3 719

    [27]

    Chang S S, Guo W H, Kim Y, Wang Y L 2013 Biophys. J. 104 313

    [28]

    Doyle A D, Wang F W, Matsumoto K, Yamada K M 2009 J. Cell. Biol. 184 481

    [29]

    Yamaguchi H, Condeelis J 2007 Biochim. Biophys. Acta. 1773 642

    [30]

    Etienne-Manneville S, Hall A 2002 Nature 420 629

    [31]

    Itoh R E, Kurokawa K, Ohba Y, Yoshizaki H, Mochizuki N, Matsuda M 2002 Mol. Cell. Biol. 22 6582

    [32]

    Srinivasan S, Wang F, Glavas S, Ott A, Hofmann F, Aktories K, Kalman D, Bourne H R 2003 J. Cell. Biol. 160 375

    [33]

    Wegner A 1976 J. Mol. Biol. 108 139

    [34]

    Fujiwara I, Takahashi S, Tadakuma H, Funatsu T, Ishiwata S 2002 Nat. Cell. Biol. 4 666

    [35]

    Welch M D, Mullins R D 2002 Annu. Rev. Cell. Dev. Biol. 18 247

    [36]

    Pollard T D, Borisy G G 2003 Cell 112 453

    [37]

    Remedios dos C G, Chhabra D, Kekic M, Dedova I V, Tsubakihara M, Berry D A, Nosworthy N J 2003 Physiol. Rev. 83 433

    [38]

    Jilkine A, Edelstein-Keshet L 2011 PLoS. Comput. Biol. 7 e1001121

    [39]

    Turing A M 1952 Philos. Trans. R. Soc. Lond. B. Biol. Sci. 2 37

    [40]

    Gierer A, Meinhardt H 1972 Kybernetik 12 30

    [41]

    Narang A 2006 J Theor. Biol. 240 538

    [42]

    Levine H, Kessler D A, Rappel W J 2006 Proc. Natl. Acad. Sci. U. S. A. 103 9761

    [43]

    Sasaki A T, Janetopoulos C, Lee S, Charest P G, Takeda K, Sundheimer L W, Meili R, Devreotes P N, Firtel R A 2007 J. Cell. Biol. 178 185

    [44]

    Weiner O D, Marganski W A, Wu L F, Altschuler S J, Kirschner M W 2007 PloS. Biol. 5 e221

    [45]

    Arai Y, Shibata T, Matsuoka S, Sato MJ, Yanagida T, Ueda M 2010 Proc. Natl. Acad. Sci. U. S. A 107 12399

    [46]

    Katsumi A, Milanini J, Kiosses W B, del Pozo M A, Kaunas R, Chien S, Hahn K M, Schwartz M A 2002 J. Cell. Biol. 158 153

    [47]

    Théry M, Racine V, Piel M, Péin A, Dimitrov A, Chen Y, Sibarita J B, Bornens M 2006 Proc. Natl. Acad. Sci. U. S. A. 103 19771

    [48]

    Huttenlocher A, Horwitz A R 2011 Cold. Spring. Harb. Perspect. Biol. 3 a005074

    [49]

    Zhu J, Luo B H, Xiao T, Zhang C, Nishida N, Springer T A 2008 Mol. Cell. 32 849

    [50]

    Wei C, Wang X, Chen M, Ouyang K, Song LS, Cheng H 2009 Nature 457 901

    [51]

    Houk A R, Jilkine A, Mejean C O, Boltyanskiy R, Dufresne E R, Angenent S B, Altschuler S J, Wu L F, Weiner O D 2012 Cell 148 175

    [52]

    Yamada K M, Cukierman E 2007 Cell 130 601

    [53]

    Truong T V, Supatto W, Koos D S, Choi J M, Fraser S E 2011 Nat. Methods. 8 757

    [54]

    Gao L, Shao L, Chen B C, Betzig E 2014 Nat. Protoc. 9 1083

    [55]

    Mahou P, Vermot J, Beaurepaire E, Supatto W 2014 Nat. Methods. 11 600

    [56]

    Hanahan D, Weinberg R A 2011 Cell 144 646

    [57]

    Kreso A, Dick J E 2014 Cell. Stem. Cell. 14 275

    [58]

    Yang G, Quan Y, Wang W, Fu Q, Wu J, Mei T, Li J, Tang Y, Luo C, Ouyang Q, Chen S, Wu L, Hei T K, Wang Y 2012 Br. J. Cancer. 106 1512

    [59]

    Gupta P B, Fillmore C M, Jiang G, Shapira S D, Tao K, Kuperwasser C, Lander E S 2011 Cell 146 633

    [60]

    Suresh S 2007 Acta. Materialia. 55 3989

  • [1] The physics-based model of AlGaN/GaN high electron mobility transistor outer fringing capacitances. Acta Physica Sinica, 2020, (): . doi: 10.7498/aps.69.20191931
  • Citation:
Metrics
  • Abstract views:  821
  • PDF Downloads:  1556
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Publishing process
  • Received Date:  02 December 2014
  • Accepted Date:  06 February 2015
  • Published Online:  05 March 2015

Application of physics in the study of cell polarity during tumor cell migration

  • 1. State Key Laboratory of Nuclear Physics and Technology, School of Physics, Peking University, Beijing 100871, China;
  • 2. Center for Quantitative Biology, Peking University, Beijing 100871, China
Fund Project:  Project supported by the National Natural Science Foundation of China (Grant No. 11434001), and the Deparment of Science of China (Grant No. 2012YQ030142).

Abstract: Investigation of tumors from a physics perspective has attracted more and more attention since the initiation, development, and metastasis of tumors are strongly influenced by the physical interactions between the tumor cells and their microenvironments. Since tumor metastasis accounts for more than 90% of cancer-associated death, one of the focuses is to understand its underlying mechanism, especially how tumor cells polarize during their migration. Cell polarization directs tumor-cell migration in response to a spatial stimulus, e.g., the gradient of chemokine or oxygen molecules. It forms the front and back edges of cells by estiblishing asymmetric distributions of cell polarity proteins such as the Rho family GTPases and organelles such as Golgi. This paper reviews how the experimental and theoretical studies combining physics with biology reveal the underlying mechanisms of cell migration and cell polarity. Experimental results demonstrate that the physics clues including extracellular matrix's mechanical properties, dimensionality, and topography are strongly coupled with the biochemical reactions to establish and maintain the cell polarity and direct cell migration. The cell migration mode in a more physiological three-dimensional (3D) matrix is different from that in a two-dimensional(2D) system. Moreover, the membrane tension is suggested to maitain cell polarity by inhibiting polarization processes outside the front edge. On the other hand, a series of reaction diffusion models have been developed to characterize cell polarity. Representative examples inculding Turing-type model, local-excitation and global-inhibition (LEGI) model, and wave-pinning model can capture certain features of cell polarization, however none of them takes the physical factors, such as the membrane tension, into account hence fails to explain previous published experimental results about the membrane tension with cell polarization. To further improve our understanding of the mechanism of cell polarity, in the future study it is experimentally important to estiblish 3D tumor systems and study the gene regulation network that can control cell polariztion by advanced microscope; theroetically it is of importance to build mathematical models for the chemical reaction diffusion systems coupled with the mechanical factors such as membarne tension. These studies will reveal the molecular mechanism of cell polarization and cell migration under a more physiological relevant condition. They may also help us understand how the higher deformation ability of cancer stem cells provides the higher migration capability compared with the normal cancer cells. Ultimately, they will facilitate developing new therapeutic strategy against tumor metastasis by targeting the signaling of tumor cells in response of physical stimuli.

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