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Heading off with the herd: how cancer cells might maneuver supernumerary centrosomes for directional migration

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Abstract

The complicity of centrosomes in carcinogenesis is unmistakable. Mounting evidence clearly implicates a robust correlation between centrosome amplification (CA) and malignant transformation in diverse tissue types. Furthermore, CA has been suggested as a marker of cancer aggressiveness, in particular the invasive phenotype, in breast and prostate cancers. One means by which CA promotes malignancy is through induction of transient spindle multipolarity during mitosis, which predisposes the cell to karyotypic changes arising from low-grade chromosome mis-segregation. It is well recognized that during cell migration in interphase, centrosome-mediated nucleation of a radial microtubule array is crucial for establishing a polarized Golgi apparatus, without which directionality is precluded. The question of how cancer cells maneuver their supernumerary centrosomes to achieve directionality during cell migration is virtually uncharted territory. Given that CA is a hallmark of cancers and has been correlated with cancer aggressiveness, malignant cells are presumably competent in managing their centrosome surfeit during directional migration, although the cellular logistics of this process remain unexplored. Another key angle worth pondering is whether an overabundance of centrosomes confers some advantage on cancer cells in terms of their migratory and invasive capabilities. Recent studies have uncovered a remarkable strategy that cancer cells employ to deal with the problem of excess centrosomes and ensure bipolar mitoses, viz., centrosome clustering. This review aims to change the narrative by exploring how an increased centrosome complement may, via aneuploidy-independent modulation of the microtubule cytoskeleton, enhance directional migration and invasion of malignant cells. We postulate that CA imbues cancer cells with cytoskeletal advantages that enhance cell polarization, Golgi-dependent vesicular trafficking, stromal invasion, and other aspects of metastatic progression. We also propose that centrosome declustering may represent a novel, cancer cell-specific antimetastatic strategy, as cancer cells may rely on centrosome clustering during migration as they do in mitosis. Elucidation of these details offers an exciting avenue for future research, as does investigating how CA may promote metastasis through enhanced directional migration.

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References

  1. D'Assoro, A. B., Lingle, W. L., & Salisbury, J. L. (2002). Centrosome amplification and the development of cancer. Oncogene, 21(40), 6146–53.

    PubMed  Google Scholar 

  2. Lingle, W. L., & Salisbury, J. L. (1999). Altered centrosome structure is associated with abnormal mitoses in human breast tumors. Am J Pathol, 155(6), 1941–51.

    PubMed  CAS  Google Scholar 

  3. Chan, J. Y. (2011). A clinical overview of centrosome amplification in human cancers. Int J Biol Sci, 7(8), 1122–44.

    PubMed  CAS  Google Scholar 

  4. Prigozhina, N. L., & Waterman-Storer, C. M. (2006). Decreased polarity and increased random motility in PtK1 epithelial cells correlate with inhibition of endosomal recycling. J Cell Sci, 119(Pt 17), 3571–82.

    PubMed  CAS  Google Scholar 

  5. Basto, R., et al. (2008). Centrosome amplification can initiate tumorigenesis in flies. Cell, 133(6), 1032–42.

    PubMed  CAS  Google Scholar 

  6. Bornens, M. (2008). Organelle positioning and cell polarity. Nature Reviews. Molecular cell biology, 9(11), 874–86.

    PubMed  CAS  Google Scholar 

  7. de Forges, H., Bouissou, A., & Perez, F. (2012). Interplay between microtubule dynamics and intracellular organization. The International Journal of Biochemistry & Cell Biology, 44(2), 266–74.

    Google Scholar 

  8. Vinogradova, T., Miller, P. M., & Kaverina, I. (2009). Microtubule network asymmetry in motile cells: role of Golgi-derived array. Cell Cycle, 8(14), 2168–74.

    PubMed  CAS  Google Scholar 

  9. Verhey, K. J., & Hammond, J. W. (2009). Traffic control: regulation of kinesin motors. Nature Reviews. Molecular Cell Biology, 10(11), 765–77.

    PubMed  CAS  Google Scholar 

  10. Siegrist, S. E., & Doe, C. Q. (2007). Microtubule-induced cortical cell polarity. Genes & Development, 21(5), 483–96.

    CAS  Google Scholar 

  11. Luxton, G. W., & Gundersen, G. G. (2011). Orientation and function of the nuclear-centrosomal axis during cell migration. Current Opinion in Cell Biology, 23(5), 579–88.

    PubMed  CAS  Google Scholar 

  12. Quinones, G. B., et al. (2011). The posttranslational modification of tubulin undergoes a switch from detyrosination to acetylation as epithelial cells become polarized. Molecular Biology of the Cell, 22(7), 1045–57.

    PubMed  CAS  Google Scholar 

  13. Silkworth, W. T., et al. (2009). Multipolar spindle pole coalescence is a major source of kinetochore mis-attachment and chromosome mis-segregation in cancer cells. PloS One, 4(8), e6564.

    PubMed  Google Scholar 

  14. Ganem, N. J., Godinho, S. A., & Pellman, D. (2009). A mechanism linking extra centrosomes to chromosomal instability. Nature, 460(7252), 278–82.

    PubMed  CAS  Google Scholar 

  15. Baccelli, I., & Trumpp, A. (2012). The evolving concept of cancer and metastasis stem cells. J Cell Biol, 198(3), 281–93.

    PubMed  CAS  Google Scholar 

  16. Lingle, W. L., et al. (2002). Centrosome amplification drives chromosomal instability in breast tumor development. Proceedings of the National Academy of Sciences of the United States of America, 99(4), 1978–83.

    PubMed  CAS  Google Scholar 

  17. Lingle, W. L., et al. (1998). Centrosome hypertrophy in human breast tumors: implications for genomic stability and cell polarity. Proc Natl Acad Sci U S A, 95(6), 2950–5.

    PubMed  CAS  Google Scholar 

  18. Yamashita, Y. M., et al. (2007). Asymmetric inheritance of mother versus daughter centrosome in stem cell division. Science, 315(5811), 518–21.

    PubMed  CAS  Google Scholar 

  19. Fukasawa, K. (2007). Oncogenes and tumour suppressors take on centrosomes. Nature reviews. Cancer, 7(12), 911–24.

    PubMed  CAS  Google Scholar 

  20. Gundersen, G. G., & Bulinski, J. C. (1988). Selective stabilization of microtubules oriented toward the direction of cell migration. Proc Natl Acad Sci U S A, 85(16), 5946–50.

    PubMed  CAS  Google Scholar 

  21. Lauffenburger, D. A., & Horwitz, A. F. (1996). Cell migration: a physically integrated molecular process. Cell, 84(3), 359–69.

    PubMed  CAS  Google Scholar 

  22. Waterman-Storer, C. M., & Salmon, E. (1999). Positive feedback interactions between microtubule and actin dynamics during cell motility. Curr Opin Cell Biol, 11(1), 61–7.

    PubMed  CAS  Google Scholar 

  23. Wittmann, T., & Waterman-Storer, C. M. (2001). Cell motility: can Rho GTPases and microtubules point the way? J Cell Sci, 114(Pt 21), 3795–803.

    PubMed  CAS  Google Scholar 

  24. Mogilner, A., & Keren, K. (2009). The shape of motile cells. Curr Biol, 19(17), R762–71.

    PubMed  CAS  Google Scholar 

  25. Ridley, A. J., et al. (2003). Cell migration: integrating signals from front to back. Science, 302(5651), 1704–9.

    PubMed  CAS  Google Scholar 

  26. Borisy, G. G., & Svitkina, T. M. (2000). Actin machinery: pushing the envelope. Curr Opin Cell Biol, 12(1), 104–12.

    PubMed  CAS  Google Scholar 

  27. Mullins, R. D., Heuser, J. A., & Pollard, T. D. (1998). The interaction of Arp2/3 complex with actin: nucleation, high affinity pointed end capping, and formation of branching networks of filaments. Proc Natl Acad Sci U S A, 95(11), 6181–6.

    PubMed  CAS  Google Scholar 

  28. Nelson, W. J. (2003). Tube morphogenesis: closure, but many openings remain. Trends Cell Biol, 13(12), 615–21.

    PubMed  CAS  Google Scholar 

  29. Vasiliev, J. M. (2004). Cytoskeletal mechanisms responsible for invasive migration of neoplastic cells. Int J Dev Biol, 48(5–6), 425–39.

    PubMed  CAS  Google Scholar 

  30. Kanchanawong, P., et al. (2010). Nanoscale architecture of integrin-based cell adhesions. Nature, 468(7323), 580–4.

    PubMed  CAS  Google Scholar 

  31. Chrzanowska-Wodnicka, M., & Burridge, K. (1996). Rho-stimulated contractility drives the formation of stress fibers and focal adhesions. J Cell Biol, 133(6), 1403–15.

    PubMed  CAS  Google Scholar 

  32. Dugina, V., et al. (2001). Focal adhesion features during myofibroblastic differentiation are controlled by intracellular and extracellular factors. J Cell Sci, 114(Pt 18), 3285–96.

    PubMed  CAS  Google Scholar 

  33. Geiger, B., & Bershadsky, A. (2002). Exploring the neighborhood: adhesion-coupled cell mechanosensors. Cell, 110(2), 139–42.

    PubMed  CAS  Google Scholar 

  34. Defilippi, P., et al. (1999). Actin cytoskeleton organization in response to integrin-mediated adhesion. Microsc Res Tech, 47(1), 67–78.

    PubMed  CAS  Google Scholar 

  35. Kaverina, I., Krylyshkina, O., & Small, J. V. (1999). Microtubule targeting of substrate contacts promotes their relaxation and dissociation. J Cell Biol, 146(5), 1033–44.

    PubMed  CAS  Google Scholar 

  36. Rid, R., et al. (2005). The last but not the least: the origin and significance of trailing adhesions in fibroblastic cells. Cell Motil Cytoskeleton, 61(3), 161–71.

    PubMed  Google Scholar 

  37. Vasiliev, J. M., et al. (2004). Rho overexpression leads to mitosis-associated detachment of cells from epithelial sheets: a link to the mechanism of cancer dissemination. Proc Natl Acad Sci U S A, 101(34), 12526–30.

    PubMed  CAS  Google Scholar 

  38. Levina, E. M., et al. (2001). Cytoskeletal control of fibroblast length: experiments with linear strips of substrate. J Cell Sci, 114(Pt 23), 4335–41.

    PubMed  CAS  Google Scholar 

  39. Kharitonova, M. A., & Vasiliev, J. M. (2008). Controlling cell length. Semin Cell Dev Biol, 19(6), 480–4.

    PubMed  Google Scholar 

  40. Rodriguez, O. C., et al. (2003). Conserved microtubule–actin interactions in cell movement and morphogenesis. Nat Cell Biol, 5(7), 599–609.

    PubMed  CAS  Google Scholar 

  41. Chang, Y. C., et al. (2008). GEF-H1 couples nocodazole-induced microtubule disassembly to cell contractility via RhoA. Mol Biol Cell, 19(5), 2147–53.

    PubMed  CAS  Google Scholar 

  42. Danowski, B. A. (1989). Fibroblast contractility and actin organization are stimulated by microtubule inhibitors. J Cell Sci, 93(Pt 2), 255–66.

    PubMed  CAS  Google Scholar 

  43. Dujardin, D. L., et al. (2003). A role for cytoplasmic dynein and LIS1 in directed cell movement. J Cell Biol, 163(6), 1205–11.

    PubMed  CAS  Google Scholar 

  44. Sutterlin, C., & Colanzi, A. (2010). The Golgi and the centrosome: building a functional partnership. J Cell Biol, 188(5), 621–8.

    PubMed  CAS  Google Scholar 

  45. Vinke, F. P., Grieve, A. G., & Rabouille, C. (2011). The multiple facets of the Golgi reassembly stacking proteins. The Biochemical Journal, 433(3), 423–33.

    PubMed  CAS  Google Scholar 

  46. Yadav, S., & Linstedt, A. D. (2011). Golgi positioning. Cold Spring Harbor Perspectives in Biology, 3, 5.

    Google Scholar 

  47. Yadav, S., Puri, S., & Linstedt, A. D. (2009). A primary role for Golgi positioning in directed secretion, cell polarity, and wound healing. Molecular biology of the cell, 20(6), 1728–36.

    PubMed  CAS  Google Scholar 

  48. Miller, P. M., et al. (2009). Golgi-derived CLASP-dependent microtubules control Golgi organization and polarized trafficking in motile cells. Nature Cell Biology, 11(9), 1069–80.

    PubMed  CAS  Google Scholar 

  49. Vinogradova, T., et al. (2012). Concerted effort of centrosomal and Golgi-derived microtubules is required for proper Golgi complex assembly but not for maintenance. Molecular Biology of the Cell, 23(5), 820–33.

    PubMed  CAS  Google Scholar 

  50. Wakida, N. M., et al. (2010). An intact centrosome is required for the maintenance of polarization during directional cell migration. PloS One, 5(12), e15462.

    PubMed  CAS  Google Scholar 

  51. Hurtado, L., et al. (2011). Disconnecting the Golgi ribbon from the centrosome prevents directional cell migration and ciliogenesis. The Journal of Cell Biology, 193(5), 917–33.

    PubMed  CAS  Google Scholar 

  52. Weaver, B. A., & Cleveland, D. W. (2007). Aneuploidy: instigator and inhibitor of tumorigenesis. Cancer Research, 67(21), 10103–5.

    PubMed  CAS  Google Scholar 

  53. Guo, H. Q., et al. (2007). Analysis of the cellular centrosome in fine-needle aspirations of the breast. Breast Cancer Research: BCR, 9(4), R48.

    PubMed  Google Scholar 

  54. Perucca-Lostanlen, D., et al. (2004). Distinct MDM2 and P14ARF expression and centrosome amplification in well-differentiated liposarcomas. Genes, Chromosomes & Cancer, 39(2), 99–109.

    CAS  Google Scholar 

  55. Gong, Y., et al. (2009). Localization of TEIF in the centrosome and its functional association with centrosome amplification in DNA damage, telomere dysfunction and human cancers. Oncogene, 28(12), 1549–60.

    PubMed  CAS  Google Scholar 

  56. Sato, N., et al. (1999). Centrosome abnormalities in pancreatic ductal carcinoma. Clinical Cancer Research: An Official Journal of the American Association for Cancer Research, 5(5), 963–70.

    CAS  Google Scholar 

  57. Yang, J., et al. (2004). Twist, a master regulator of morphogenesis, plays an essential role in tumor metastasis. Cell, 117(7), 927–39.

    PubMed  CAS  Google Scholar 

  58. Ingber, D. E., Madri, J. A., & Jamieson, J. D. (1981). Role of basal lamina in neoplastic disorganization of tissue architecture. Proc Natl Acad Sci U S A, 78(6), 3901–5.

    PubMed  CAS  Google Scholar 

  59. Lozano, E., Betson, M., & Braga, V. M. (2003). Tumor progression: small GTPases and loss of cell–cell adhesion. Bioessays, 25(5), 452–63.

    PubMed  CAS  Google Scholar 

  60. Ridley, A. J. (2006). Rho GTPases and actin dynamics in membrane protrusions and vesicle trafficking. Trends Cell Biol, 16(10), 522–9.

    PubMed  CAS  Google Scholar 

  61. Pihan, G. A., et al. (2001). Centrosome defects can account for cellular and genetic changes that characterize prostate cancer progression. Cancer Res, 61(5), 2212–9.

    PubMed  CAS  Google Scholar 

  62. Lingle, W. L., et al. (2002). Centrosome amplification drives chromosomal instability in breast tumor development. Proc Natl Acad Sci U S A, 99(4), 1978–83.

    PubMed  CAS  Google Scholar 

  63. Bissell, M. J. (2007). Modelling molecular mechanisms of breast cancer and invasion: lessons from the normal gland. Biochem Soc Trans, 35(Pt 1), 18–22.

    PubMed  CAS  Google Scholar 

  64. Yilmaz, M., & Christofori, G. (2009). EMT, the cytoskeleton, and cancer cell invasion. Cancer Metastasis Rev, 28(1–2), 15–33.

    PubMed  Google Scholar 

  65. Petroll, W. M., & Ma, L. (2003). Direct, dynamic assessment of cell–matrix interactions inside fibrillar collagen lattices. Cell Motil Cytoskeleton, 55(4), 254–64.

    PubMed  Google Scholar 

  66. Friedl, P., & Wolf, K. (2009). Proteolytic interstitial cell migration: a five-step process. Cancer Metastasis Rev, 28(1–2), 129–35.

    PubMed  Google Scholar 

  67. Wang, W., et al. (2002). Single cell behavior in metastatic primary mammary tumors correlated with gene expression patterns revealed by molecular profiling. Cancer Res, 62(21), 6278–88.

    PubMed  CAS  Google Scholar 

  68. Ketema, M., & Sonnenberg, A. (2011). Nesprin-3: a versatile connector between the nucleus and the cytoskeleton. Biochem Soc Trans, 39(6), 1719–24.

    PubMed  CAS  Google Scholar 

  69. Khatau, S. B., et al. (2012). The differential formation of the LINC-mediated perinuclear actin cap in pluripotent and somatic cells. PLoS One, 7(5), e36689.

    PubMed  CAS  Google Scholar 

  70. Vasiliev, J. M., et al. (1970). Effect of colcemid on the locomotory behaviour of fibroblasts. J Embryol Exp Morphol, 24(3), 625–40.

    PubMed  CAS  Google Scholar 

  71. Bershadsky, A. D., Vaisberg, E. A., & Vasiliev, J. M. (1991). Pseudopodial activity at the active edge of migrating fibroblast is decreased after drug-induced microtubule depolymerization. Cell Motil Cytoskeleton, 19(3), 152–8.

    PubMed  CAS  Google Scholar 

  72. Malech, H. L., Root, R. K., & Gallin, J. I. (1977). Structural analysis of human neutrophil migration. Centriole, microtubule, and microfilament orientation and function during chemotaxis. J Cell Biol, 75(3), 666–93.

    PubMed  CAS  Google Scholar 

  73. Gierke, S., & Wittmann, T. (2012). EB1-recruited microtubule + TIP complexes coordinate protrusion dynamics during 3D epithelial remodeling. Curr Biol, 22(9), 753–62.

    PubMed  CAS  Google Scholar 

  74. Sumiyoshi, E., & Sugimoto, A. (2012). Cell polarity: centrosomes release signals for polarization. Curr Biol, 22(8), R281–3.

    PubMed  CAS  Google Scholar 

  75. Block, M. R., et al. (2008). Podosome-type adhesions and focal adhesions, so alike yet so different. Eur J Cell Biol, 87(8–9), 491–506.

    PubMed  CAS  Google Scholar 

  76. Nakahara, H., et al. (1998). Activation of beta1 integrin signaling stimulates tyrosine phosphorylation of p190RhoGAP and membrane-protrusive activities at invadopodia. J Biol Chem, 273(1), 9–12.

    PubMed  CAS  Google Scholar 

  77. Schoumacher, M., et al. (2010). Actin, microtubules, and vimentin intermediate filaments cooperate for elongation of invadopodia. J Cell Biol, 189(3), 541–56.

    PubMed  CAS  Google Scholar 

  78. Kikuchi, K., & Takahashi, K. (2008). WAVE2- and microtubule-dependent formation of long protrusions and invasion of cancer cells cultured on three-dimensional extracellular matrices. Cancer Sci, 99(11), 2252–9.

    PubMed  CAS  Google Scholar 

  79. Schnaeker, E. M., et al. (2004). Microtubule-dependent matrix metalloproteinase-2/matrix metalloproteinase-9 exocytosis: prerequisite in human melanoma cell invasion. Cancer Res, 64(24), 8924–31.

    PubMed  CAS  Google Scholar 

  80. Sbai, O., et al. (2008). Vesicular trafficking and secretion of matrix metalloproteinases-2, -9 and tissue inhibitor of metalloproteinases-1 in neuronal cells. Mol Cell Neurosci, 39(4), 549–68.

    PubMed  CAS  Google Scholar 

  81. Sbai, O., et al. (2010). Differential vesicular distribution and trafficking of MMP-2, MMP-9, and their inhibitors in astrocytes. Glia, 58(3), 344–66.

    PubMed  Google Scholar 

  82. Hanania, R., et al. (2012). Classically activated macrophages use stable microtubules for matrix metalloproteinase-9 (MMP-9) secretion. J Biol Chem, 287(11), 8468–83.

    PubMed  CAS  Google Scholar 

  83. Takino, T., et al. (2006). Membrane-type 1 matrix metalloproteinase modulates focal adhesion stability and cell migration. Exp Cell Res, 312(8), 1381–9.

    PubMed  CAS  Google Scholar 

  84. Takino, T., et al. (2007). Inhibition of membrane-type 1 matrix metalloproteinase at cell–matrix adhesions. Cancer Res, 67(24), 11621–9.

    PubMed  CAS  Google Scholar 

  85. Wang, Y., & McNiven, M. A. (2012). Invasive matrix degradation at focal adhesions occurs via protease recruitment by a FAK-p130Cas complex. J Cell Biol, 196(3), 375–85.

    PubMed  CAS  Google Scholar 

  86. Bissell, M. J., & Radisky, D. (2001). Putting tumours in context. Nat Rev Cancer, 1(1), 46–54.

    PubMed  CAS  Google Scholar 

  87. Paget, S. (1989). The distribution of secondary growths in cancer of the breast. 1889. Cancer Metastasis Rev, 8(2), 98–101.

    PubMed  CAS  Google Scholar 

  88. Erler, J. T., & Weaver, V. M. (2009). Three-dimensional context regulation of metastasis. Clin Exp Metastasis, 26(1), 35–49.

    PubMed  Google Scholar 

  89. Bhowmick, N. A., & Moses, H. L. (2005). Tumor-stroma interactions. Curr Opin Genet Dev, 15(1), 97–101.

    PubMed  CAS  Google Scholar 

  90. Bosman, F. T., & Stamenkovic, I. (2003). Functional structure and composition of the extracellular matrix. J Pathol, 200(4), 423–8.

    PubMed  CAS  Google Scholar 

  91. Kumar, S., & Weaver, V. M. (2009). Mechanics, malignancy, and metastasis: the force journey of a tumor cell. Cancer Metastasis Rev, 28(1–2), 113–27.

    PubMed  Google Scholar 

  92. Paszek, M. J., et al. (2005). Tensional homeostasis and the malignant phenotype. Cancer Cell, 8(3), 241–54.

    PubMed  CAS  Google Scholar 

  93. Reno, F., et al. (2002). Release and activation of matrix metalloproteinase-9 during in vitro mechanical compression in hypertrophic scars. Arch Dermatol, 138(4), 475–8.

    PubMed  CAS  Google Scholar 

  94. Friedl, P., & Wolf, K. (2003). Tumour-cell invasion and migration: diversity and escape mechanisms. Nature reviews. Cancer, 3(5), 362–74.

    PubMed  CAS  Google Scholar 

  95. Belletti, B., et al. (2010). p27kip1 controls cell morphology and motility by regulating microtubule-dependent lipid raft recycling. Mol Cell Biol, 30(9), 2229–40.

    PubMed  CAS  Google Scholar 

  96. Berton, S., et al. (2009). The tumor suppressor functions of p27(kip1) include control of the mesenchymal/amoeboid transition. Mol Cell Biol, 29(18), 5031–45.

    PubMed  CAS  Google Scholar 

  97. Bartolini, F., & Gundersen, G. G. (2010). Formins and microtubules. Biochim Biophys Acta, 1803(2), 164–73.

    PubMed  CAS  Google Scholar 

  98. Gaillard, J., et al. (2011). Differential interactions of the formins INF2, mDia1, and mDia2 with microtubules. Mol Biol Cell, 22(23), 4575–87.

    PubMed  CAS  Google Scholar 

  99. Goode, B. L., & Eck, M. J. (2007). Mechanism and function of formins in the control of actin assembly. Annu Rev Biochem, 76, 593–627.

    PubMed  CAS  Google Scholar 

  100. Lutolf, M. P., & Hubbell, J. A. (2005). Synthetic biomaterials as instructive extracellular microenvironments for morphogenesis in tissue engineering. Nat Biotechnol, 23(1), 47–55.

    PubMed  CAS  Google Scholar 

  101. Hiraoka, N., et al. (1998). Matrix metalloproteinases regulate neovascularization by acting as pericellular fibrinolysins. Cell, 95(3), 365–77.

    PubMed  CAS  Google Scholar 

  102. Chun, J., et al. (2003). Cultures of ligament fibroblasts in fibrin matrix gel. Connect Tissue Res, 44(2), 81–7.

    PubMed  CAS  Google Scholar 

  103. Sabeh, F., et al. (2004). Tumor cell traffic through the extracellular matrix is controlled by the membrane-anchored collagenase MT1-MMP. J Cell Biol, 167(4), 769–81.

    PubMed  CAS  Google Scholar 

  104. Filippov, S., et al. (2005). MT1-matrix metalloproteinase directs arterial wall invasion and neointima formation by vascular smooth muscle cells. J Exp Med, 202(5), 663–71.

    PubMed  CAS  Google Scholar 

  105. Gaggioli, C., et al. (2007). Fibroblast-led collective invasion of carcinoma cells with differing roles for RhoGTPases in leading and following cells. Nat Cell Biol, 9(12), 1392–400.

    PubMed  CAS  Google Scholar 

  106. Nagano, S., et al. (2008). Cancer cell death enhances the penetration and efficacy of oncolytic herpes simplex virus in tumors. Cancer Res, 68(10), 3795–802.

    PubMed  CAS  Google Scholar 

  107. Trepat, X., & Fredberg, J. J. (2011). Plithotaxis and emergent dynamics in collective cellular migration. Trends Cell Biol, 21(11), 638–46.

    PubMed  CAS  Google Scholar 

  108. Hegerfeldt, Y., et al. (2002). Collective cell movement in primary melanoma explants: plasticity of cell–cell interaction, beta1-integrin function, and migration strategies. Cancer Research, 62(7), 2125–30.

    PubMed  CAS  Google Scholar 

  109. Friedl, P., & Gilmour, D. (2009). Collective cell migration in morphogenesis, regeneration and cancer. Nature Reviews. Molecular Cell Biology, 10(7), 445–57.

    PubMed  CAS  Google Scholar 

  110. Hockel, M., & Vaupel, P. (2001). Tumor hypoxia: definitions and current clinical, biologic, and molecular aspects. J Natl Cancer Inst, 93(4), 266–76.

    PubMed  CAS  Google Scholar 

  111. Klein, A., Flugel, D., & Kietzmann, T. (2008). Transcriptional regulation of serine/threonine kinase-15 (STK15) expression by hypoxia and HIF-1. Mol Biol Cell, 19(9), 3667–75.

    PubMed  CAS  Google Scholar 

  112. Katayama, H., et al. (2001). Interaction and feedback regulation between STK15/BTAK/Aurora-A kinase and protein phosphatase 1 through mitotic cell division cycle. J Biol Chem, 276(49), 46219–24.

    PubMed  CAS  Google Scholar 

  113. Condeelis, J., & Pollard, J. W. (2006). Macrophages: obligate partners for tumor cell migration, invasion, and metastasis. Cell, 124(2), 263–6.

    PubMed  CAS  Google Scholar 

  114. Glinskii, A. B., et al. (2003). Viable circulating metastatic cells produced in orthotopic but not ectopic prostate cancer models. Cancer Res, 63(14), 4239–43.

    PubMed  CAS  Google Scholar 

  115. Whipple, R. A., et al. (2008). Vimentin filaments support extension of tubulin-based microtentacles in detached breast tumor cells. Cancer Res, 68(14), 5678–88.

    PubMed  CAS  Google Scholar 

  116. Matrone, M. A., et al. (2010). Microtentacles tip the balance of cytoskeletal forces in circulating tumor cells. Cancer Res, 70(20), 7737–41.

    PubMed  CAS  Google Scholar 

  117. Whipple, R. A., Cheung, A. M., & Martin, S. S. (2007). Detyrosinated microtubule protrusions in suspended mammary epithelial cells promote reattachment. Exp Cell Res, 313(7), 1326–36.

    PubMed  CAS  Google Scholar 

  118. Kramer, A., Maier, B., & Bartek, J. (2011). Centrosome clustering and chromosomal (in)stability: a matter of life and death. Mol Oncol, 5(4), 324–35.

    PubMed  Google Scholar 

  119. Ogden, A., P.C. Rida, and R. Aneja (2012) Let's huddle to prevent a muddle: centrosome declustering as an attractive anticancer strategy. Cell Death Differ 19:1255–1267

    Google Scholar 

  120. Grinberg-Rashi, H., et al. (2009). The expression of three genes in primary non-small cell lung cancer is associated with metastatic spread to the brain. Clinical Cancer Research: An Official Journal of the American Association for Cancer Research, 15(5), 1755–61.

    CAS  Google Scholar 

  121. Kraljevic Pavelic, S., et al.,(2011) Metastasis: new perspectives on an old problem. Molecular cancer, 10: p. 22

  122. Kurokawa, K., et al. (2005). Mechanism and role of localized activation of Rho-family GTPases in growth factor-stimulated fibroblasts and neuronal cells. Biochem Soc Trans, 33(Pt 4), 631–4.

    PubMed  CAS  Google Scholar 

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Ogden, A., Rida, P.C.G. & Aneja, R. Heading off with the herd: how cancer cells might maneuver supernumerary centrosomes for directional migration. Cancer Metastasis Rev 32, 269–287 (2013). https://doi.org/10.1007/s10555-012-9413-5

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  • DOI: https://doi.org/10.1007/s10555-012-9413-5

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