Emerging Biological Principles of Metastasis

Cell

Volumn 168, Issue 4, 2017, Pages 670-691

  Lambert, Arthur W ^a   Pattabiraman, Diwakar R ^a   Weinberg, Robert A ^a,b  

^a WHITEHEAD INSTITUTE FOR BIOMEDICAL RESEARCH   (United States)

^b MASSACHUSETTS INSTITUTE OF TECHNOLOGY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

CANCER STEM CELL; CARCINOMA CELL; CELL FATE; CELL GROWTH; CELL INTERACTION; CELL INVASION; CELL MIGRATION; CIRCULATING TUMOR CELL; EPIGENETICS; EPITHELIAL MESENCHYMAL TRANSITION; EXTRAVASATION; HUMAN; METASTASIS; NEUTROPHIL; NONHUMAN; PRIMARY TUMOR; PRIORITY JOURNAL; REVIEW; STEM CELL NICHE; THROMBOCYTE; TUMOR MICROENVIRONMENT; ANIMAL; CARCINOMA; CELL MOTION; GENETICS; IMMUNOLOGY; METABOLISM; NEOPLASM; PATHOLOGY; T LYMPHOCYTE; TUMOR EMBOLISM; TUMOR INVASION;

ANIMALS; BLOOD PLATELETS; CARCINOMA; CELL MOVEMENT; EPITHELIAL-MESENCHYMAL TRANSITION; HUMANS; NEOPLASM INVASIVENESS; NEOPLASM METASTASIS; NEOPLASMS; NEOPLASTIC CELLS, CIRCULATING; NEUTROPHILS; T-LYMPHOCYTES; TUMOR MICROENVIRONMENT;

EID: 85012054684     PISSN: 00928674     EISSN: 10974172     Source Type: Journal    
DOI: 10.1016/j.cell.2016.11.037     Document Type: Review

References (205)

1. Aceto, N., Bardia, A., Miyamoto, D.T., Donaldson, M.C., Wittner, B.S., Spencer, J.A., Yu, M., Pely, A., Engstrom, A., Zhu, H., et al. Circulating tumor cell clusters are oligoclonal precursors of breast cancer metastasis. Cell 158 (2014), 1110–1122.
2. Aceto, N., Toner, M., Maheswaran, S., Haber, D.A., En Route to Metastasis: Circulating Tumor Cell Clusters and Epithelial-to-Mesenchymal Transition. Trends Cancer 1 (2015), 44–52.
3. Acharyya, S., Oskarsson, T., Vanharanta, S., Malladi, S., Kim, J., Morris, P.G., Manova-Todorova, K., Leversha, M., Hogg, N., Seshan, V.E., et al. A CXCL1 paracrine network links cancer chemoresistance and metastasis. Cell 150 (2012), 165–178.
4. Aguirre-Ghiso, J.A., Models, mechanisms and clinical evidence for cancer dormancy. Nat. Rev. Cancer 7 (2007), 834–846.
5. Aguirre Ghiso, J.A., Kovalski, K., Ossowski, L., Tumor dormancy induced by downregulation of urokinase receptor in human carcinoma involves integrin and MAPK signaling. J. Cell Biol. 147 (1999), 89–104.
6. Al-Mehdi, A.B., Tozawa, K., Fisher, A.B., Shientag, L., Lee, A., Muschel, R.J., Intravascular origin of metastasis from the proliferation of endothelium-attached tumor cells: a new model for metastasis. Nat. Med. 6 (2000), 100–102.
7. Alluri, P.G., Speers, C., Chinnaiyan, A.M., Estrogen receptor mutations and their role in breast cancer progression. Breast Cancer Res., 16, 2014, 494.
8. Au, S.H., Storey, B.D., Moore, J.C., Tang, Q., Chen, Y.L., Javaid, S., Sarioglu, A.F., Sullivan, R., Madden, M.W., O'Keefe, R., et al. Clusters of circulating tumor cells traverse capillary-sized vessels. Proc. Natl. Acad. Sci. USA 113 (2016), 4947–4952.
9. Baccelli, I., Schneeweiss, A., Riethdorf, S., Stenzinger, A., Schillert, A., Vogel, V., Klein, C., Saini, M., Bäuerle, T., Wallwiener, M., et al. Identification of a population of blood circulating tumor cells from breast cancer patients that initiates metastasis in a xenograft assay. Nat. Biotechnol. 31 (2013), 539–544.
10. Balic, M., Lin, H., Young, L., Hawes, D., Giuliano, A., McNamara, G., Datar, R.H., Cote, R.J., Most early disseminated cancer cells detected in bone marrow of breast cancer patients have a putative breast cancer stem cell phenotype. Clin. Cancer Res. 12 (2006), 5615–5621.
11. Barkan, D., Kleinman, H., Simmons, J.L., Asmussen, H., Kamaraju, A.K., Hoenorhoff, M.J., Liu, Z.Y., Costes, S.V., Cho, E.H., Lockett, S., et al. Inhibition of metastatic outgrowth from single dormant tumor cells by targeting the cytoskeleton. Cancer Res. 68 (2008), 6241–6250.
12. Barkan, D., El Touny, L.H., Michalowski, A.M., Smith, J.A., Chu, I., Davis, A.S., Webster, J.D., Hoover, S., Simpson, R.M., Gauldie, J., Green, J.E., Metastatic growth from dormant cells induced by a col-I-enriched fibrotic environment. Cancer Res. 70 (2010), 5706–5716.
13. Bednarz-Knoll, N., Alix-Panabières, C., Pantel, K., Plasticity of disseminating cancer cells in patients with epithelial malignancies. Cancer Metastasis Rev. 31 (2012), 673–687.
14. Bidwell, B.N., Slaney, C.Y., Withana, N.P., Forster, S., Cao, Y., Loi, S., Andrews, D., Mikeska, T., Mangan, N.E., Samarajiwa, S.A., et al. Silencing of Irf7 pathways in breast cancer cells promotes bone metastasis through immune escape. Nat. Med. 18 (2012), 1224–1231.
15. Bonapace, L., Coissieux, M.M., Wyckoff, J., Mertz, K.D., Varga, Z., Junt, T., Bentires-Alj, M., Cessation of CCL2 inhibition accelerates breast cancer metastasis by promoting angiogenesis. Nature 515 (2014), 130–133.
16. Bonnomet, A., Syne, L., Brysse, A., Feyereisen, E., Thompson, E.W., Noël, A., Foidart, J.M., Birembaut, P., Polette, M., Gilles, C., A dynamic in vivo model of epithelial-to-mesenchymal transitions in circulating tumor cells and metastases of breast cancer. Oncogene 31 (2012), 3741–3753.
17. Bos, P.D., Zhang, X.H., Nadal, C., Shu, W., Gomis, R.R., Nguyen, D.X., Minn, A.J., van de Vijver, M.J., Gerald, W.L., Foekens, J.A., Massagué, J., Genes that mediate breast cancer metastasis to the brain. Nature 459 (2009), 1005–1009.
18. Brabletz, T., To differentiate or not–routes towards metastasis. Nat. Rev. Cancer 12 (2012), 425–436.
19. Brabletz, T., Jung, A., Spaderna, S., Hlubek, F., Kirchner, T., Opinion: migrating cancer stem cells - an integrated concept of malignant tumour progression. Nat. Rev. Cancer 5 (2005), 744–749.
20. Bragado, P., Estrada, Y., Parikh, F., Krause, S., Capobianco, C., Farina, H.G., Schewe, D.M., Aguirre-Ghiso, J.A., TGF-β2 dictates disseminated tumour cell fate in target organs through TGF-β-RIII and p38α/β signalling. Nat. Cell Biol. 15 (2013), 1351–1361.
21. Braun, S., Vogl, F.D., Naume, B., Janni, W., Osborne, M.P., Coombes, R.C., Schlimok, G., Diel, I.J., Gerber, B., Gebauer, G., et al. A pooled analysis of bone marrow micrometastasis in breast cancer. N. Engl. J. Med. 353 (2005), 793–802.
22. Cairns, J., Mutation selection and the natural history of cancer. Nature 255 (1975), 197–200.
23. Campbell, P.J., Yachida, S., Mudie, L.J., Stephens, P.J., Pleasance, E.D., Stebbings, L.A., Morsberger, L.A., Latimer, C., McLaren, S., Lin, M.L., et al. The patterns and dynamics of genomic instability in metastatic pancreatic cancer. Nature 467 (2010), 1109–1113.
24. Celià-Terrassa, T., Meca-Cortés, O., Mateo, F., Martínez de Paz, A., Rubio, N., Arnal-Estapé, A., Ell, B.J., Bermudo, R., Díaz, A., Guerra-Rebollo, M., et al. Epithelial-mesenchymal transition can suppress major attributes of human epithelial tumor-initiating cells. J. Clin. Invest. 122 (2012), 1849–1868.
25. Chambers, A.F., Groom, A.C., MacDonald, I.C., Dissemination and growth of cancer cells in metastatic sites. Nat. Rev. Cancer 2 (2002), 563–572.
26. Chen, Q., Zhang, X.H., Massagué, J., Macrophage binding to receptor VCAM-1 transmits survival signals in breast cancer cells that invade the lungs. Cancer Cell 20 (2011), 538–549.
27. Chen, Q., Boire, A., Jin, X., Valiente, M., Er, E.E., Lopez-Soto, A., Jacob, L.S., Patwa, R., Shah, H., Xu, K., et al. Carcinoma-astrocyte gap junctions promote brain metastasis by cGAMP transfer. Nature 533 (2016), 493–498.
28. Cheung, K.J., Gabrielson, E., Werb, Z., Ewald, A.J., Collective invasion in breast cancer requires a conserved basal epithelial program. Cell 155 (2013), 1639–1651.
29. Cheung, K.J., Padmanaban, V., Silvestri, V., Schipper, K., Cohen, J.D., Fairchild, A.N., Gorin, M.A., Verdone, J.E., Pienta, K.J., Bader, J.S., Ewald, A.J., Polyclonal breast cancer metastases arise from collective dissemination of keratin 14-expressing tumor cell clusters. Proc. Natl. Acad. Sci. USA 113 (2016), E854–E863.
30. Chung, Y.C., Wei, W.C., Hung, C.N., Kuo, J.F., Hsu, C.P., Chang, K.J., Chao, W.T., Rab11 collaborates E-cadherin to promote collective cell migration and indicates a poor prognosis in colorectal carcinoma. Eur. J. Clin. Invest. 46 (2016), 1002–1011.
31. Clever, D., Roychoudhuri, R., Constantinides, M.G., Askenase, M.H., Sukumar, M., Klebanoff, C.A., Eil, R.L., Hickman, H.D., Yu, Z., Pan, J.H., et al. Oxygen sensing by T cells establishes an immunologically tolerant metastatic niche. Cell 166 (2016), 1117–1131.
32. Coffelt, S.B., Kersten, K., Doornebal, C.W., Weiden, J., Vrijland, K., Hau, C.S., Verstegen, N.J., Ciampricotti, M., Hawinkels, L.J., Jonkers, J., de Visser, K.E., IL-17-producing γδ T cells and neutrophils conspire to promote breast cancer metastasis. Nature 522 (2015), 345–348.
33. Coffelt, S.B., Wellenstein, M.D., de Visser, K.E., Neutrophils in cancer: neutral no more. Nat. Rev. Cancer 16 (2016), 431–446.
34. Cools-Lartigue, J., Spicer, J., McDonald, B., Gowing, S., Chow, S., Giannias, B., Bourdeau, F., Kubes, P., Ferri, L., Neutrophil extracellular traps sequester circulating tumor cells and promote metastasis. J. Clin. Invest. 123 (2013), 3446–3458.
35. Costa-Silva, B., Aiello, N.M., Ocean, A.J., Singh, S., Zhang, H., Thakur, B.K., Becker, A., Hoshino, A., Mark, M.T., Molina, H., et al. Pancreatic cancer exosomes initiate pre-metastatic niche formation in the liver. Nat. Cell Biol. 17 (2015), 816–826.
36. Cox, T.R., Erler, J.T., Molecular pathways: connecting fibrosis and solid tumor metastasis. Clin. Cancer Res. 20 (2014), 3637–3643.
37. de Boer, M., van Dijck, J.A., Bult, P., Borm, G.F., Tjan-Heijnen, V.C., Breast cancer prognosis and occult lymph node metastases, isolated tumor cells, and micrometastases. J. Natl. Cancer Inst. 102 (2010), 410–425.
38. De Cock, J.M., Shibue, T., Dongre, A., Keckesova, Z., Reinhardt, F., Weinberg, R.A., Inflammation triggers Zeb1-dependent escape from tumor latency. Cancer Res. 76 (2016), 6778–6784.
39. De Craene, B., Berx, G., Regulatory networks defining EMT during cancer initiation and progression. Nat. Rev. Cancer 13 (2013), 97–110.
40. Del Pozo Martin, Y., Park, D., Ramachandran, A., Ombrato, L., Calvo, F., Chakravarty, P., Spencer-Dene, B., Derzsi, S., Hill, C.S., Sahai, E., Malanchi, I., Mesenchymal cancer cell-stroma crosstalk promotes niche activation, epithelial reversion, and metastatic colonization. Cell Rep. 13 (2015), 2456–2469.
41. Denny, S.K., Yang, D., Chuang, C.H., Brady, J.J., Lim, J.S., Grüner, B.M., Chiou, S.H., Schep, A.N., Baral, J., Hamard, C., et al. Nfib promotes metastasis through a widespread increase in chromatin accessibility. Cell 166 (2016), 328–342.
42. Ding, L., Ellis, M.J., Li, S., Larson, D.E., Chen, K., Wallis, J.W., Harris, C.C., McLellan, M.D., Fulton, R.S., Fulton, L.L., et al. Genome remodelling in a basal-like breast cancer metastasis and xenograft. Nature 464 (2010), 999–1005.
43. Douma, S., Van Laar, T., Zevenhoven, J., Meuwissen, R., Van Garderen, E., Peeper, D.S., Suppression of anoikis and induction of metastasis by the neurotrophic receptor TrkB. Nature 430 (2004), 1034–1039.
44. El Touny, L.H., Vieira, A., Mendoza, A., Khanna, C., Hoenerhoff, M.J., Green, J.E., Combined SFK/MEK inhibition prevents metastatic outgrowth of dormant tumor cells. J. Clin. Invest. 124 (2014), 156–168.
45. Erler, J.T., Bennewith, K.L., Nicolau, M., Dornhöfer, N., Kong, C., Le, Q.T., Chi, J.T., Jeffrey, S.S., Giaccia, A.J., Lysyl oxidase is essential for hypoxia-induced metastasis. Nature 440 (2006), 1222–1226.
46. Erler, J.T., Bennewith, K.L., Cox, T.R., Lang, G., Bird, D., Koong, A., Le, Q.T., Giaccia, A.J., Hypoxia-induced lysyl oxidase is a critical mediator of bone marrow cell recruitment to form the premetastatic niche. Cancer Cell 15 (2009), 35–44.
47. Eyles, J., Puaux, A.-L., Wang, X., Toh, B., Prakash, C., Hong, M., Tan, T.G., Zheng, L., Ong, L.C., Jin, Y., et al. Tumor cells disseminate early, but immunosurveillance limits metastatic outgrowth, in a mouse model of melanoma. J. Clin. Invest. 120 (2010), 2030–2039.
48. Fan, F., Samuel, S., Evans, K.W., Lu, J., Xia, L., Zhou, Y., Sceusi, E., Tozzi, F., Ye, X.C., Mani, S.A., Ellis, L.M., Overexpression of snail induces epithelial-mesenchymal transition and a cancer stem cell-like phenotype in human colorectal cancer cells. Cancer Med. 1 (2012), 5–16.
49. Fearon, E.R., Vogelstein, B., A genetic model for colorectal tumorigenesis. Cell 61 (1990), 759–767.
50. Fidler, I.J., The pathogenesis of cancer metastasis: the ‘seed and soil’ hypothesis revisited. Nat. Rev. Cancer 3 (2003), 453–458.
51. Fischer, K.R., Durrans, A., Lee, S., Sheng, J., Li, F., Wong, S.T., Choi, H., El Rayes, T., Ryu, S., Troeger, J., et al. Epithelial-to-mesenchymal transition is not required for lung metastasis but contributes to chemoresistance. Nature 527 (2015), 472–476.
52. Franco, A.T., Corken, A., Ware, J., Platelets at the interface of thrombosis, inflammation, and cancer. Blood 126 (2015), 582–588.
53. Fridlender, Z.G., Sun, J., Kim, S., Kapoor, V., Cheng, G., Ling, L., Worthen, G.S., Albelda, S.M., Polarization of tumor-associated neutrophil phenotype by TGF-beta: “N1” versus “N2” TAN. Cancer Cell 16 (2009), 183–194.
54. Friedl, P., Locker, J., Sahai, E., Segall, J.E., Classifying collective cancer cell invasion. Nat. Cell Biol. 14 (2012), 777–783.
55. Gaggioli, C., Hooper, S., Hidalgo-Carcedo, C., Grosse, R., Marshall, J.F., Harrington, K., Sahai, E., Fibroblast-led collective invasion of carcinoma cells with differing roles for RhoGTPases in leading and following cells. Nat. Cell Biol. 9 (2007), 1392–1400.
56. Gao, H., Chakraborty, G., Lee-Lim, A.P., Mo, Q., Decker, M., Vonica, A., Shen, R., Brogi, E., Brivanlou, A.H., Giancotti, F.G., The BMP inhibitor Coco reactivates breast cancer cells at lung metastatic sites. Cell 150 (2012), 764–779.
57. Gao, H., Chakraborty, G., Zhang, Z., Akalay, I., Gadiya, M., Gao, Y., Sinha, S., Hu, J., Jiang, C., Akram, M., et al. Multi-organ site metastatic reactivation mediated by non-canonical discoidin domain receptor 1 signaling. Cell 166 (2016), 47–62.
58. Garraway, L.A., Lander, E.S., Lessons from the cancer genome. Cell 153 (2013), 17–37.
59. Gasic, G.J., Gasic, T.B., Stewart, C.C., Antimetastatic effects associated with platelet reduction. Proc. Natl. Acad. Sci. USA 61 (1968), 46–52.
60. Gay, L.J., Felding-Habermann, B., Contribution of platelets to tumour metastasis. Nat. Rev. Cancer 11 (2011), 123–134.
61. Gazdar, A.F., Activating and resistance mutations of EGFR in non-small-cell lung cancer: role in clinical response to EGFR tyrosine kinase inhibitors. Oncogene 28:Suppl 1 (2009), S24–S31.
62. Gerlinger, M., Rowan, A.J., Horswell, S., Larkin, J., Endesfelder, D., Gronroos, E., Martinez, P., Matthews, N., Stewart, A., Tarpey, P., et al. Intratumor heterogeneity and branched evolution revealed by multiregion sequencing. N. Engl. J. Med. 366 (2012), 883–892.
63. Ghajar, C.M., Metastasis prevention by targeting the dormant niche. Nat. Rev. Cancer 15 (2015), 238–247.
64. Ghajar, C.M., Peinado, H., Mori, H., Matei, I.R., Evason, K.J., Brazier, H., Almeida, D., Koller, A., Hajjar, K.A., Stainier, D.Y., et al. The perivascular niche regulates breast tumour dormancy. Nat. Cell Biol. 15 (2013), 807–817.
65. Giancotti, F.G., Mechanisms governing metastatic dormancy and reactivation. Cell 155 (2013), 750–764.
66. Gilbert, L.A., Hemann, M.T., DNA damage-mediated induction of a chemoresistant niche. Cell 143 (2010), 355–366.
67. Goss, P.E., Chambers, A.F., Does tumour dormancy offer a therapeutic target?. Nat. Rev. Cancer 10 (2010), 871–877.
68. Granot, Z., Henke, E., Comen, E.A., King, T.A., Norton, L., Benezra, R., Tumor entrained neutrophils inhibit seeding in the premetastatic lung. Cancer Cell 20 (2011), 300–314.
69. Grosse-Wilde, A., Fouquier d'Hérouël, A., McIntosh, E., Ertaylan, G., Skupin, A., Kuestner, R.E., del Sol, A., Walters, K.A., Huang, S., Stemness of the hybrid epithelial/mesenchymal state in breast cancer and its association with poor survival. PLoS ONE, 10, 2015, e0126522.
70. Gundem, G., Van Loo, P., Kremeyer, B., Alexandrov, L.B., Tubio, J.M., Papaemmanuil, E., Brewer, D.S., Kallio, H.M., Högnäs, G., Annala, M., et al., ICGC Prostate UK Group. The evolutionary history of lethal metastatic prostate cancer. Nature 520 (2015), 353–357.
71. Gupta, G.P., Massagué, J., Cancer metastasis: building a framework. Cell 127 (2006), 679–695.
72. Gupta, P.B., Kuperwasser, C., Brunet, J.P., Ramaswamy, S., Kuo, W.L., Gray, J.W., Naber, S.P., Weinberg, R.A., The melanocyte differentiation program predisposes to metastasis after neoplastic transformation. Nat. Genet. 37 (2005), 1047–1054.
73. Gupta, G.P., Nguyen, D.X., Chiang, A.C., Bos, P.D., Kim, J.Y., Nadal, C., Gomis, R.R., Manova-Todorova, K., Massagué, J., Mediators of vascular remodelling co-opted for sequential steps in lung metastasis. Nature 446 (2007), 765–770.
74. Gupta, P.B., Onder, T.T., Jiang, G., Tao, K., Kuperwasser, C., Weinberg, R.A., Lander, E.S., Identification of selective inhibitors of cancer stem cells by high-throughput screening. Cell 138 (2009), 645–659.
75. Haffner, M.C., Mosbruger, T., Esopi, D.M., Fedor, H., Heaphy, C.M., Walker, D.A., Adejola, N., Gürel, M., Hicks, J., Meeker, A.K., et al. Tracking the clonal origin of lethal prostate cancer. J. Clin. Invest. 123 (2013), 4918–4922.
76. Hanahan, D., Coussens, L.M., Accessories to the crime: functions of cells recruited to the tumor microenvironment. Cancer Cell 21 (2012), 309–322.
77. Hanahan, D., Weinberg, R.A., The hallmarks of cancer. Cell 100 (2000), 57–70.
78. Hanahan, D., Weinberg, R.A., Hallmarks of cancer: the next generation. Cell 144 (2011), 646–674.
79. Harper, K.L., Sosa, M.S., Entenberg, D., Hosseini, H., Cheung, J.F., Nobre, R., Avivar-Valderas, A., Nagi, C., Girnius, N., Davis, R.J., et al. Mechanism of early dissemination and metastasis in Her2+ mammary cancer. Nature, 2016, 10.1038/nature20609 Published online December 14, 2016.
80. Headley, M.B., Bins, A., Nip, A., Roberts, E.W., Looney, M.R., Gerard, A., Krummel, M.F., Visualization of immediate immune responses to pioneer metastatic cells in the lung. Nature 531 (2016), 513–517.
81. Hong, T., Watanabe, K., Ta, C.H., Villarreal-Ponce, A., Nie, Q., Dai, X., An Ovol2-Zeb1 mutual inhibitory circuit governs bidirectional and multi-step transition between epithelial and mesenchymal states. PLoS Comput. Biol., 11, 2015, e1004569.
82. Hosseini, H., Obradović, M.M., Hoffmann, M., Harper, K.L., Sosa, M.S., Werner-Klein, M., Nanduri, L.K., Werno, C., Ehrl, C., Maneck, M., et al. Early dissemination seeds metastasis in breast cancer. Nature, 2016, 10.1038/nature20785 Published online December 14, 2016.
83. Huh, S.J., Liang, S., Sharma, A., Dong, C., Robertson, G.P., Transiently entrapped circulating tumor cells interact with neutrophils to facilitate lung metastasis development. Cancer Res. 70 (2010), 6071–6082.
84. Hüsemann, Y., Geigl, J.B., Schubert, F., Musiani, P., Meyer, M., Burghart, E., Forni, G., Eils, R., Fehm, T., Riethmüller, G., Klein, C.A., Systemic spread is an early step in breast cancer. Cancer Cell 13 (2008), 58–68.
85. Ince, T.A., Richardson, A.L., Bell, G.W., Saitoh, M., Godar, S., Karnoub, A.E., Iglehart, J.D., Weinberg, R.A., Transformation of different human breast epithelial cell types leads to distinct tumor phenotypes. Cancer Cell 12 (2007), 160–170.
86. Jacob, L.S., Vanharanta, S., Obenauf, A.C., Pirun, M., Viale, A., Socci, N.D., Massagué, J., Metastatic competence can emerge with selection of preexisting oncogenic alleles without a need of new mutations. Cancer Res. 75 (2015), 3713–3719.
87. Jordan, N.V., Johnson, G.L., Abell, A.N., Tracking the intermediate stages of epithelial-mesenchymal transition in epithelial stem cells and cancer. Cell Cycle 10 (2011), 2865–2873.
88. Kalluri, R., Weinberg, R.A., The basics of epithelial-mesenchymal transition. J. Clin. Invest. 119 (2009), 1420–1428.
89. Kang, Y., Pantel, K., Tumor cell dissemination: emerging biological insights from animal models and cancer patients. Cancer Cell 23 (2013), 573–581.
90. Kaplan, R.N., Riba, R.D., Zacharoulis, S., Bramley, A.H., Vincent, L., Costa, C., MacDonald, D.D., Jin, D.K., Shido, K., Kerns, S.A., et al. VEGFR1-positive haematopoietic bone marrow progenitors initiate the pre-metastatic niche. Nature 438 (2005), 820–827.
91. Karaman, S., Detmar, M., Mechanisms of lymphatic metastasis. J. Clin. Invest. 124 (2014), 922–928.
92. Kienast, Y., von Baumgarten, L., Fuhrmann, M., Klinkert, W.E., Goldbrunner, R., Herms, J., Winkler, F., Real-time imaging reveals the single steps of brain metastasis formation. Nat. Med. 16 (2010), 116–122.
93. Kitamura, T., Qian, B.Z., Pollard, J.W., Immune cell promotion of metastasis. Nat. Rev. Immunol. 15 (2015), 73–86.
94. Klein, C.A., Parallel progression of primary tumours and metastases. Nat. Rev. Cancer 9 (2009), 302–312.
95. Kobayashi, A., Okuda, H., Xing, F., Pandey, P.R., Watabe, M., Hirota, S., Pai, S.K., Liu, W., Fukuda, K., Chambers, C., et al. Bone morphogenetic protein 7 in dormancy and metastasis of prostate cancer stem-like cells in bone. J. Exp. Med. 208 (2011), 2641–2655.
96. Koebel, C.M., Vermi, W., Swann, J.B., Zerafa, N., Rodig, S.J., Old, L.J., Smyth, M.J., Schreiber, R.D., Adaptive immunity maintains occult cancer in an equilibrium state. Nature 450 (2007), 903–907.
97. Köhler, S., Ullrich, S., Richter, U., Schumacher, U., E-/P-selectins and colon carcinoma metastasis: first in vivo evidence for their crucial role in a clinically relevant model of spontaneous metastasis formation in the lung. Br. J. Cancer 102 (2010), 602–609.
98. Kong, D., Banerjee, S., Ahmad, A., Li, Y., Wang, Z., Sethi, S., Sarkar, F.H., Epithelial to mesenchymal transition is mechanistically linked with stem cell signatures in prostate cancer cells. PLoS ONE, 5, 2010, e12445.
99. Kopp, H.G., Placke, T., Salih, H.R., Platelet-derived transforming growth factor-beta down-regulates NKG2D thereby inhibiting natural killer cell antitumor reactivity. Cancer Res. 69 (2009), 7775–7783.
100. Korpal, M., Ell, B.J., Buffa, F.M., Ibrahim, T., Blanco, M.A., Celià-Terrassa, T., Mercatali, L., Khan, Z., Goodarzi, H., Hua, Y., et al. Direct targeting of Sec23a by miR-200s influences cancer cell secretome and promotes metastatic colonization. Nat. Med. 17 (2011), 1101–1108.
101. Kurrey, N.K., Jalgaonkar, S.P., Joglekar, A.V., Ghanate, A.D., Chaskar, P.D., Doiphode, R.Y., Bapat, S.A., Snail and slug mediate radioresistance and chemoresistance by antagonizing p53-mediated apoptosis and acquiring a stem-like phenotype in ovarian cancer cells. Stem Cells 27 (2009), 2059–2068.
102. Labelle, M., Hynes, R.O., The initial hours of metastasis: the importance of cooperative host-tumor cell interactions during hematogenous dissemination. Cancer Discov. 2 (2012), 1091–1099.
103. Labelle, M., Begum, S., Hynes, R.O., Direct signaling between platelets and cancer cells induces an epithelial-mesenchymal-like transition and promotes metastasis. Cancer Cell 20 (2011), 576–590.
104. Labelle, M., Begum, S., Hynes, R.O., Platelets guide the formation of early metastatic niches. Proc. Natl. Acad. Sci. USA 111 (2014), E3053–E3061.
105. Lamouille, S., Xu, J., Derynck, R., Molecular mechanisms of epithelial-mesenchymal transition. Nat. Rev. Mol. Cell Biol. 15 (2014), 178–196.
106. Latil, M., Nassar, D., Beck, B., Boumahdi, S., Wang, L., Brisebarre, A., Dubois, C., Nkusi, E., Lenglez, S., Checinska, A., et al. Cell-Type-Specific Chromatin States Differentially Prime Squamous Cell Carcinoma Tumor-Initiating Cells for Epithelial to Mesenchymal Transition. Cell Stem Cell, 2016, 10.1016/j.stem.2016.10.018 Published online November 16, 2016.
107. Lawson, D.A., Bhakta, N.R., Kessenbrock, K., Prummel, K.D., Yu, Y., Takai, K., Zhou, A., Eyob, H., Balakrishnan, S., Wang, C.Y., et al. Single-cell analysis reveals a stem-cell program in human metastatic breast cancer cells. Nature 526 (2015), 131–135.
108. Lee, H.J., Zhuang, G., Cao, Y., Du, P., Kim, H.J., Settleman, J., Drug resistance via feedback activation of Stat3 in oncogene-addicted cancer cells. Cancer Cell 26 (2014), 207–221.
109. Levental, K.R., Yu, H., Kass, L., Lakins, J.N., Egeblad, M., Erler, J.T., Fong, S.F., Csiszar, K., Giaccia, A., Weninger, W., et al. Matrix crosslinking forces tumor progression by enhancing integrin signaling. Cell 139 (2009), 891–906.
110. Li, W., Kang, Y., Probing the fifty shades of EMT in metastasis. Trends Cancer 2 (2016), 65–67.
111. Li, C.M., Gocheva, V., Oudin, M.J., Bhutkar, A., Wang, S.Y., Date, S.R., Ng, S.R., Whittaker, C.A., Bronson, R.T., Snyder, E.L., et al. Foxa2 and Cdx2 cooperate with Nkx2-1 to inhibit lung adenocarcinoma metastasis. Genes Dev. 29 (2015), 1850–1862.
112. Lim, E., Vaillant, F., Wu, D., Forrest, N.C., Pal, B., Hart, A.H., Asselin-Labat, M.L., Gyorki, D.E., Ward, T., Partanen, A., et al., kConFab. Aberrant luminal progenitors as the candidate target population for basal tumor development in BRCA1 mutation carriers. Nat. Med. 15 (2009), 907–913.
113. Liu, W., Laitinen, S., Khan, S., Vihinen, M., Kowalski, J., Yu, G., Chen, L., Ewing, C.M., Eisenberger, M.A., Carducci, M.A., et al. Copy number analysis indicates monoclonal origin of lethal metastatic prostate cancer. Nat. Med. 15 (2009), 559–565.
114. Long, H., Xiang, T., Qi, W., Huang, J., Chen, J., He, L., Liang, Z., Guo, B., Li, Y., Xie, R., Zhu, B., CD133+ ovarian cancer stem-like cells promote non-stem cancer cell metastasis via CCL5 induced epithelial-mesenchymal transition. Oncotarget 6 (2015), 5846–5859.
115. Loo, J.M., Scherl, A., Nguyen, A., Man, F.Y., Weinberg, E., Zeng, Z., Saltz, L., Paty, P.B., Tavazoie, S.F., Extracellular metabolic energetics can promote cancer progression. Cell 160 (2015), 393–406.
116. Lu, X., Mu, E., Wei, Y., Riethdorf, S., Yang, Q., Yuan, M., Yan, J., Hua, Y., Tiede, B.J., Lu, X., et al. VCAM-1 promotes osteolytic expansion of indolent bone micrometastasis of breast cancer by engaging α4β1-positive osteoclast progenitors. Cancer Cell 20 (2011), 701–714.
117. Lundgren, K., Nordenskjöld, B., Landberg, G., Hypoxia, Snail and incomplete epithelial-mesenchymal transition in breast cancer. Br. J. Cancer 101 (2009), 1769–1781.
118. Luzzi, K.J., MacDonald, I.C., Schmidt, E.E., Kerkvliet, N., Morris, V.L., Chambers, A.F., Groom, A.C., Multistep nature of metastatic inefficiency: dormancy of solitary cells after successful extravasation and limited survival of early micrometastases. Am. J. Pathol. 153 (1998), 865–873.
119. Malanchi, I., Santamaria-Martínez, A., Susanto, E., Peng, H., Lehr, H.A., Delaloye, J.F., Huelsken, J., Interactions between cancer stem cells and their niche govern metastatic colonization. Nature 481 (2011), 85–89.
120. Malladi, S., Macalinao, D.G., Jin, X., He, L., Basnet, H., Zou, Y., de Stanchina, E., Massagué, J., Metastatic latency and immune evasion through autocrine inhibition of WNT. Cell 165 (2016), 45–60.
121. Mani, S.A., Guo, W., Liao, M.J., Eaton, E.N., Ayyanan, A., Zhou, A.Y., Brooks, M., Reinhard, F., Zhang, C.C., Shipitsin, M., et al. The epithelial-mesenchymal transition generates cells with properties of stem cells. Cell 133 (2008), 704–715.
122. Marusyk, A., Almendro, V., Polyak, K., Intra-tumour heterogeneity: a looking glass for cancer?. Nat. Rev. Cancer 12 (2012), 323–334.
123. McAllister, S.S., Weinberg, R.A., The tumour-induced systemic environment as a critical regulator of cancer progression and metastasis. Nat. Cell Biol. 16 (2014), 717–727.
124. Miyamoto, D.T., Zheng, Y., Wittner, B.S., Lee, R.J., Zhu, H., Broderick, K.T., Desai, R., Fox, D.B., Brannigan, B.W., Trautwein, J., et al. RNA-Seq of single prostate CTCs implicates noncanonical Wnt signaling in antiandrogen resistance. Science 349 (2015), 1351–1356.
125. Molyneux, G., Geyer, F.C., Magnay, F.A., McCarthy, A., Kendrick, H., Natrajan, R., Mackay, A., Grigoriadis, A., Tutt, A., Ashworth, A., et al. BRCA1 basal-like breast cancers originate from luminal epithelial progenitors and not from basal stem cells. Cell Stem Cell 7 (2010), 403–417.
126. Morel, A.P., Lièvre, M., Thomas, C., Hinkal, G., Ansieau, S., Puisieux, A., Generation of breast cancer stem cells through epithelial-mesenchymal transition. PLoS ONE, 3, 2008, e2888.
127. Mouw, J.K., Yui, Y., Damiano, L., Bainer, R.O., Lakins, J.N., Acerbi, I., Ou, G., Wijekoon, A.C., Levental, K.R., Gilbert, P.M., et al. Tissue mechanics modulate microRNA-dependent PTEN expression to regulate malignant progression. Nat. Med. 20 (2014), 360–367.
128. Müller-Hermelink, N., Braumüller, H., Pichler, B., Wieder, T., Mailhammer, R., Schaak, K., Ghoreschi, K., Yazdi, A., Haubner, R., Sander, C.A., et al. TNFR1 signaling and IFN-γ signaling determine whether T cells induce tumor dormancy or promote multistage carcinogenesis. Cancer Cell 13 (2008), 507–518.
129. Mundy, G.R., Metastasis to bone: causes, consequences and therapeutic opportunities. Nat. Rev. Cancer 2 (2002), 584–593.
130. Naxerova, K., Jain, R.K., Using tumour phylogenetics to identify the roots of metastasis in humans. Nat. Rev. Clin. Oncol. 12 (2015), 258–272.
131. Nguyen, D.X., Bos, P.D., Massagué, J., Metastasis: from dissemination to organ-specific colonization. Nat. Rev. Cancer 9 (2009), 274–284.
132. Nieswandt, B., Hafner, M., Echtenacher, B., Männel, D.N., Lysis of tumor cells by natural killer cells in mice is impeded by platelets. Cancer Res. 59 (1999), 1295–1300.
133. Nieto, M.A., Huang, R.Y., Jackson, R.A., Thiery, J.P., EMT: 2016. Cell 166 (2016), 21–45.
134. Nowell, P.C., The clonal evolution of tumor cell populations. Science 194 (1976), 23–28.
135. Obenauf, A.C., Massague, J., Surviving at a distance: organ specific metastasis. Trends Cancer 1 (2015), 76–91.
136. Obenauf, A.C., Zou, Y., Ji, A.L., Vanharanta, S., Shu, W., Shi, H., Kong, X., Bosenberg, M.C., Wiesner, T., Rosen, N., et al. Therapy-induced tumour secretomes promote resistance and tumour progression. Nature 520 (2015), 368–372.
137. Ocaña, O.H., Córcoles, R., Fabra, A., Moreno-Bueno, G., Acloque, H., Vega, S., Barrallo-Gimeno, A., Cano, A., Nieto, M.A., Metastatic colonization requires the repression of the epithelial-mesenchymal transition inducer Prrx1. Cancer Cell 22 (2012), 709–724.
138. Oskarsson, T., Acharyya, S., Zhang, X.H., Vanharanta, S., Tavazoie, S.F., Morris, P.G., Downey, R.J., Manova-Todorova, K., Brogi, E., Massagué, J., Breast cancer cells produce tenascin C as a metastatic niche component to colonize the lungs. Nat. Med. 17 (2011), 867–874.
139. Oskarsson, T., Batlle, E., Massagué, J., Metastatic stem cells: sources, niches, and vital pathways. Cell Stem Cell 14 (2014), 306–321.
140. Ozturk, S., Papageorgis, P., Wong, C.K., Lambert, A.W., Abdolmaleky, H.M., Thiagalingam, A., Cohen, H.T., Thiagalingam, S., SDPR functions as a metastasis suppressor in breast cancer by promoting apoptosis. Proc. Natl. Acad. Sci. USA 113 (2016), 638–643.
141. Padua, D., Zhang, X.H., Wang, Q., Nadal, C., Gerald, W.L., Gomis, R.R., Massagué, J., TGFbeta primes breast tumors for lung metastasis seeding through angiopoietin-like 4. Cell 133 (2008), 66–77.
142. Palumbo, J.S., Talmage, K.E., Massari, J.V., La Jeunesse, C.M., Flick, M.J., Kombrinck, K.W., Jirousková, M., Degen, J.L., Platelets and fibrin(ogen) increase metastatic potential by impeding natural killer cell-mediated elimination of tumor cells. Blood 105 (2005), 178–185.
143. Palumbo, J.S., Talmage, K.E., Massari, J.V., La Jeunesse, C.M., Flick, M.J., Kombrinck, K.W., Hu, Z., Barney, K.A., Degen, J.L., Tumor cell-associated tissue factor and circulating hemostatic factors cooperate to increase metastatic potential through natural killer cell-dependent and-independent mechanisms. Blood 110 (2007), 133–141.
144. Pang, R., Law, W.L., Chu, A.C., Poon, J.T., Lam, C.S., Chow, A.K., Ng, L., Cheung, L.W., Lan, X.R., Lan, H.Y., et al. A subpopulation of CD26+ cancer stem cells with metastatic capacity in human colorectal cancer. Cell Stem Cell 6 (2010), 603–615.
145. Peinado, H., Alečković, M., Lavotshkin, S., Matei, I., Costa-Silva, B., Moreno-Bueno, G., Hergueta-Redondo, M., Williams, C., García-Santos, G., Ghajar, C., et al. Melanoma exosomes educate bone marrow progenitor cells toward a pro-metastatic phenotype through MET. Nat. Med. 18 (2012), 883–891.
146. Piskounova, E., Agathocleous, M., Murphy, M.M., Hu, Z., Huddlestun, S.E., Zhao, Z., Leitch, A.M., Johnson, T.M., DeBerardinis, R.J., Morrison, S.J., Oxidative stress inhibits distant metastasis by human melanoma cells. Nature 527 (2015), 186–191.
147. Podsypanina, K., Du, Y.C., Jechlinger, M., Beverly, L.J., Hambardzumyan, D., Varmus, H., Seeding and propagation of untransformed mouse mammary cells in the lung. Science 321 (2008), 1841–1844.
148. Proia, T.A., Keller, P.J., Gupta, P.B., Klebba, I., Jones, A.D., Sedic, M., Gilmore, H., Tung, N., Naber, S.P., Schnitt, S., et al. Genetic predisposition directs breast cancer phenotype by dictating progenitor cell fate. Cell Stem Cell 8 (2011), 149–163.
149. Psaila, B., Lyden, D., The metastatic niche: adapting the foreign soil. Nat. Rev. Cancer 9 (2009), 285–293.
150. Qian, B., Deng, Y., Im, J.H., Muschel, R.J., Zou, Y., Li, J., Lang, R.A., Pollard, J.W., A distinct macrophage population mediates metastatic breast cancer cell extravasation, establishment and growth. PLoS ONE, 4, 2009, e6562.
151. Qian, B.Z., Li, J., Zhang, H., Kitamura, T., Zhang, J., Campion, L.R., Kaiser, E.A., Snyder, L.A., Pollard, J.W., CCL2 recruits inflammatory monocytes to facilitate breast-tumour metastasis. Nature 475 (2011), 222–225.
152. Quail, D.F., Joyce, J.A., Microenvironmental regulation of tumor progression and metastasis. Nat. Med. 19 (2013), 1423–1437.
153. Rankin, E.B., Giaccia, A.J., Hypoxic control of metastasis. Science 352 (2016), 175–180.
154. Rasheed, Z.A., Yang, J., Wang, Q., Kowalski, J., Freed, I., Murter, C., Hong, S.M., Koorstra, J.B., Rajeshkumar, N.V., He, X., et al. Prognostic significance of tumorigenic cells with mesenchymal features in pancreatic adenocarcinoma. J. Natl. Cancer Inst. 102 (2010), 340–351.
155. Revenu, C., Gilmour, D., EMT 2.0: shaping epithelia through collective migration. Curr. Opin. Genet. Dev. 19 (2009), 338–342.
156. Reymond, N., d’Água, B.B., Ridley, A.J., Crossing the endothelial barrier during metastasis. Nat. Rev. Cancer 13 (2013), 858–870.
157. Rhim, A.D., Mirek, E.T., Aiello, N.M., Maitra, A., Bailey, J.M., McAllister, F., Reichert, M., Beatty, G.L., Rustgi, A.K., Vonderheide, R.H., et al. EMT and dissemination precede pancreatic tumor formation. Cell 148 (2012), 349–361.
158. Ross, J.B., Huh, D., Noble, L.B., Tavazoie, S.F., Identification of molecular determinants of primary and metastatic tumour re-initiation in breast cancer. Nat. Cell Biol. 17 (2015), 651–664.
159. Sagiv, J.Y., Michaeli, J., Assi, S., Mishalian, I., Kisos, H., Levy, L., Damti, P., Lumbroso, D., Polyansky, L., Sionov, R.V., et al. Phenotypic diversity and plasticity in circulating neutrophil subpopulations in cancer. Cell Rep. 10 (2015), 562–573.
160. Sampson, V.B., David, J.M., Puig, I., Patil, P.U., de Herreros, A.G., Thomas, G.V., Rajasekaran, A.K., Wilms’ tumor protein induces an epithelial-mesenchymal hybrid differentiation state in clear cell renal cell carcinoma. PLoS ONE, 9, 2014, e102041.
161. Schliekelman, M.J., Taguchi, A., Zhu, J., Dai, X., Rodriguez, J., Celiktas, M., Zhang, Q., Chin, A., Wong, C.H., Wang, H., et al. Molecular portraits of epithelial, mesenchymal, and hybrid states in lung adenocarcinoma and their relevance to survival. Cancer Res. 75 (2015), 1789–1800.
162. Schumacher, D., Strilic, B., Sivaraj, K.K., Wettschureck, N., Offermanns, S., Platelet-derived nucleotides promote tumor-cell transendothelial migration and metastasis via P2Y2 receptor. Cancer Cell 24 (2013), 130–137.
163. Sethi, N., Kang, Y., Unravelling the complexity of metastasis - molecular understanding and targeted therapies. Nat. Rev. Cancer 11 (2011), 735–748.
164. Sevenich, L., Bowman, R.L., Mason, S.D., Quail, D.F., Rapaport, F., Elie, B.T., Brogi, E., Brastianos, P.K., Hahn, W.C., Holsinger, L.J., et al. Analysis of tumour- and stroma-supplied proteolytic networks reveals a brain-metastasis-promoting role for cathepsin S. Nat. Cell Biol. 16 (2014), 876–888.
165. Sharma, P., Allison, J.P., Immune checkpoint targeting in cancer therapy: toward combination strategies with curative potential. Cell 161 (2015), 205–214.
166. Shibue, T., Weinberg, R.A., Integrin beta1-focal adhesion kinase signaling directs the proliferation of metastatic cancer cells disseminated in the lungs. Proc. Natl. Acad. Sci. USA 106 (2009), 10290–10295.
167. Shibue, T., Brooks, M.W., Inan, M.F., Reinhardt, F., Weinberg, R.A., The outgrowth of micrometastases is enabled by the formation of filopodium-like protrusions. Cancer Discov. 2 (2012), 706–721.
168. Shibue, T., Brooks, M.W., Weinberg, R.A., An integrin-linked machinery of cytoskeletal regulation that enables experimental tumor initiation and metastatic colonization. Cancer Cell 24 (2013), 481–498.
169. Shiozawa, Y., Pedersen, E.A., Havens, A.M., Jung, Y., Mishra, A., Joseph, J., Kim, J.K., Patel, L.R., Ying, C., Ziegler, A.M., et al. Human prostate cancer metastases target the hematopoietic stem cell niche to establish footholds in mouse bone marrow. J. Clin. Invest. 121 (2011), 1298–1312.
170. Singh, A., Settleman, J., EMT, cancer stem cells and drug resistance: an emerging axis of evil in the war on cancer. Oncogene 29 (2010), 4741–4751.
171. Skobe, M., Hawighorst, T., Jackson, D.G., Prevo, R., Janes, L., Velasco, P., Riccardi, L., Alitalo, K., Claffey, K., Detmar, M., Induction of tumor lymphangiogenesis by VEGF-C promotes breast cancer metastasis. Nat. Med. 7 (2001), 192–198.
172. Sosa, M.S., Avivar-Valderas, A., Bragado, P., Wen, H.C., Aguirre-Ghiso, J.A., ERK1/2 and p38α/β signaling in tumor cell quiescence: opportunities to control dormant residual disease. Clin. Cancer Res. 17 (2011), 5850–5857.
173. Sosa, M.S., Bragado, P., Aguirre-Ghiso, J.A., Mechanisms of disseminated cancer cell dormancy: an awakening field. Nat. Rev. Cancer 14 (2014), 611–622.
174. Spicer, J.D., McDonald, B., Cools-Lartigue, J.J., Chow, S.C., Giannias, B., Kubes, P., Ferri, L.E., Neutrophils promote liver metastasis via Mac-1-mediated interactions with circulating tumor cells. Cancer Res. 72 (2012), 3919–3927.
175. Spiegel, A., Brooks, M.W., Houshyar, S., Reinhardt, F., Ardolino, M., Fessler, E., Chen, M.B., Krall, J.A., DeCock, J., Zervantonakis, I.K., et al. Neutrophils suppress intraluminal NK cell-mediated tumor cell clearance and enhance extravasation of disseminated carcinoma cells. Cancer Discov. 6 (2016), 630–649.
176. Steeg, P.S., Metastasis suppressors alter the signal transduction of cancer cells. Nat. Rev. Cancer 3 (2003), 55–63.
177. Steeg, P.S., Targeting metastasis. Nat. Rev. Cancer 16 (2016), 201–218.
178. Straussman, R., Morikawa, T., Shee, K., Barzily-Rokni, M., Qian, Z.R., Du, J., Davis, A., Mongare, M.M., Gould, J., Frederick, D.T., et al. Tumour micro-environment elicits innate resistance to RAF inhibitors through HGF secretion. Nature 487 (2012), 500–504.
179. Strilic, B., Yang, L., Albarrán-Juárez, J., Wachsmuth, L., Han, K., Müller, U.C., Pasparakis, M., Offermanns, S., Tumour-cell-induced endothelial cell necroptosis via death receptor 6 promotes metastasis. Nature 536 (2016), 215–218.
180. Sun, Y., Campisi, J., Higano, C., Beer, T.M., Porter, P., Coleman, I., True, L., Nelson, P.S., Treatment-induced damage to the tumor microenvironment promotes prostate cancer therapy resistance through WNT16B. Nat. Med. 18 (2012), 1359–1368.
181. Talmadge, J.E., Fidler, I.J., AACR centennial series: the biology of cancer metastasis: historical perspective. Cancer Res. 70 (2010), 5649–5669.
182. Thiery, J.P., Epithelial-mesenchymal transitions in tumour progression. Nat. Rev. Cancer 2 (2002), 442–454.
183. Trimboli, A.J., Fukino, K., de Bruin, A., Wei, G., Shen, L., Tanner, S.M., Creasap, N., Rosol, T.J., Robinson, M.L., Eng, C., et al. Direct evidence for epithelial-mesenchymal transitions in breast cancer. Cancer Res. 68 (2008), 937–945.
184. Tsai, J.H., Donaher, J.L., Murphy, D.A., Chau, S., Yang, J., Spatiotemporal regulation of epithelial-mesenchymal transition is essential for squamous cell carcinoma metastasis. Cancer Cell 22 (2012), 725–736.
185. Turajlic, S., Swanton, C., Metastasis as an evolutionary process. Science 352 (2016), 169–175.
186. Valiente, M., Obenauf, A.C., Jin, X., Chen, Q., Zhang, X.H., Lee, D.J., Chaft, J.E., Kris, M.G., Huse, J.T., Brogi, E., Massagué, J., Serpins promote cancer cell survival and vascular co-option in brain metastasis. Cell 156 (2014), 1002–1016.
187. Vanharanta, S., Massagué, J., Origins of metastatic traits. Cancer Cell 24 (2013), 410–421.
188. Veracini, L., Grall, D., Schaub, S., Beghelli-de la Forest Divonne, S., Etienne-Grimaldi, M.C., Milano, G., Bozec, A., Babin, E., Sudaka, A., Thariat, J., Van Obberghen-Schilling, E., Elevated Src family kinase activity stabilizes E-cadherin-based junctions and collective movement of head and neck squamous cell carcinomas. Oncotarget 6 (2015), 7570–7583.
189. Vogelstein, B., Papadopoulos, N., Velculescu, V.E., Zhou, S., Diaz, L.A. Jr., Kinzler, K.W., Cancer genome landscapes. Science 339 (2013), 1546–1558.
190. Wan, L., Pantel, K., Kang, Y., Tumor metastasis: moving new biological insights into the clinic. Nat. Med. 19 (2013), 1450–1464.
191. Wculek, S.K., Malanchi, I., Neutrophils support lung colonization of metastasis-initiating breast cancer cells. Nature 528 (2015), 413–417.
192. Weilbaecher, K.N., Guise, T.A., McCauley, L.K., Cancer to bone: a fatal attraction. Nat. Rev. Cancer 11 (2011), 411–425.
193. Weng, D., Penzner, J.H., Song, B., Koido, S., Calderwood, S.K., Gong, J., Metastasis is an early event in mouse mammary carcinomas and is associated with cells bearing stem cell markers. Breast Cancer Res., 14, 2012, R18.
194. Westcott, J.M., Prechtl, A.M., Maine, E.A., Dang, T.T., Esparza, M.A., Sun, H., Zhou, Y., Xie, Y., Pearson, G.W., An epigenetically distinct breast cancer cell subpopulation promotes collective invasion. J. Clin. Invest. 125 (2015), 1927–1943.
195. Winslow, M.M., Dayton, T.L., Verhaak, R.G., Kim-Kiselak, C., Snyder, E.L., Feldser, D.M., Hubbard, D.D., DuPage, M.J., Whittaker, C.A., Hoersch, S., et al. Suppression of lung adenocarcinoma progression by Nkx2-1. Nature 473 (2011), 101–104.
196. Wolf, M.J., Hoos, A., Bauer, J., Boettcher, S., Knust, M., Weber, A., Simonavicius, N., Schneider, C., Lang, M., Stürzl, M., et al. Endothelial CCR2 signaling induced by colon carcinoma cells enables extravasation via the JAK2-Stat5 and p38MAPK pathway. Cancer Cell 22 (2012), 91–105.
197. Yachida, S., Jones, S., Bozic, I., Antal, T., Leary, R., Fu, B., Kamiyama, M., Hruban, R.H., Eshleman, J.R., Nowak, M.A., et al. Distant metastasis occurs late during the genetic evolution of pancreatic cancer. Nature 467 (2010), 1114–1117.
198. Yates, L.R., Gerstung, M., Knappskog, S., Desmedt, C., Gundem, G., Van Loo, P., Aas, T., Alexandrov, L.B., Larsimont, D., Davies, H., et al. Subclonal diversification of primary breast cancer revealed by multiregion sequencing. Nat. Med. 21 (2015), 751–759.
199. Ye, X., Tam, W.L., Shibue, T., Kaygusuz, Y., Reinhardt, F., Ng Eaton, E., Weinberg, R.A., Distinct EMT programs control normal mammary stem cells and tumour-initiating cells. Nature 525 (2015), 256–260.
200. Yu, M., Ting, D.T., Stott, S.L., Wittner, B.S., Ozsolak, F., Paul, S., Ciciliano, J.C., Smas, M.E., Winokur, D., Gilman, A.J., et al. RNA sequencing of pancreatic circulating tumour cells implicates WNT signalling in metastasis. Nature 487 (2012), 510–513.
201. Yu, M., Bardia, A., Wittner, B.S., Stott, S.L., Smas, M.E., Ting, D.T., Isakoff, S.J., Ciciliano, J.C., Wells, M.N., Shah, A.M., et al. Circulating breast tumor cells exhibit dynamic changes in epithelial and mesenchymal composition. Science 339 (2013), 580–584.
202. Yu, M., Bardia, A., Aceto, N., Bersani, F., Madden, M.W., Donaldson, M.C., Desai, R., Zhu, H., Comaills, V., Zheng, Z., et al. Cancer therapy. Ex vivo culture of circulating breast tumor cells for individualized testing of drug susceptibility. Science 345 (2014), 216–220.
203. Zhang, X.H., Wang, Q., Gerald, W., Hudis, C.A., Norton, L., Smid, M., Foekens, J.A., Massagué, J., Latent bone metastasis in breast cancer tied to Src-dependent survival signals. Cancer Cell 16 (2009), 67–78.
204. Zheng, X., Carstens, J.L., Kim, J., Scheible, M., Kaye, J., Sugimoto, H., Wu, C.C., LeBleu, V.S., Kalluri, R., Epithelial-to-mesenchymal transition is dispensable for metastasis but induces chemoresistance in pancreatic cancer. Nature 527 (2015), 525–530.
205. Zhou, D., Kannappan, V., Chen, X., Li, J., Leng, X., Zhang, J., Xuan, S., RBP2 induces stem-like cancer cells by promoting EMT and is a prognostic marker for renal cell carcinoma. Exp. Mol. Med., 48, 2016, e238.