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Journal of Oncology
Volume 2011 (2011), Article ID 591427, 7 pages
http://dx.doi.org/10.1155/2011/591427
Review Article

Cooperation of Cancer Stem Cell Properties and Epithelial-Mesenchymal Transition in the Establishment of Breast Cancer Metastasis

1Department of Surgery, Keio University School of Medicine, 35 Shinanomachi, Shinjyuku, Tokyo 160-8582, Japan
2Department of Surgery, International University of Health and Welfare, 1-4-3 Mita, Minatoku, Tokyo 108-8329, Japan

Received 1 September 2010; Revised 9 November 2010; Accepted 2 December 2010

Academic Editor: Aurelio Lorico

Copyright © 2011 Tetsu Hayashida et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Linked References

  1. D. Weinstat-Saslow and P. S. Steeg, “Angiogenesis and colonization in the tumor metastatic process: basic and applied advances,” FASEB Journal, vol. 8, no. 6, pp. 401–407, 1994. View at Scopus
  2. I. J. Fidler and L. M. Ellis, “The implications of angiogenesis for the biology and therapy of cancer metastasis,” Cell, vol. 79, no. 2, pp. 185–188, 1994. View at Publisher · View at Google Scholar · View at Scopus
  3. M. Herlyn and S. B. Malkowicz, “Biology of disease. Regulatory pathways in tumor growth and invasion,” Laboratory Investigation, vol. 65, no. 3, pp. 262–271, 1991. View at Scopus
  4. E. C. Woodhouse, R. F. Chuaqui, and L. A. Liotta, “General mechanisms of metastasis,” Cancer, vol. 80, no. 8, pp. 1529–1537, 1997. View at Scopus
  5. A. F. Chambers, A. C. Groom, and I. C. MacDonald, “Dissemination and growth of cancer cells in metastatic sites,” Nature Reviews Cancer, vol. 2, no. 8, pp. 563–572, 2002. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  6. E. W. Thompson, D. F. Newgreen, and D. Tarin, “Carcinoma invasion and metastasis: a role for epithelial-mesenchymal transition?” Cancer Research, vol. 65, no. 14, pp. 5991–5995, 2005. View at Scopus
  7. H. Hugo, M. L. Ackland, T. Blick, M. G. Lawrence, J. A. Clements, E. D. Williams, and E. W. Thompson, “Epithelial—mesenchymal and mesenchymal—epithelial transitions in carcinoma progression,” Journal of Cellular Physiology, vol. 213, no. 2, pp. 374–383, 2007. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  8. K. Polyak and R. A. Weinberg, “Transitions between epithelial and mesenchymal states: acquisition of malignant and stem cell traits,” Nature Reviews Cancer, vol. 9, no. 4, pp. 265–273, 2009. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  9. M. Al-Hajj, M. S. Wicha, A. Benito-Hernandez, S. J. Morrison, and M. F. Clarke, “Prospective identification of tumorigenic breast cancer cells,” Proceedings of the National Academy of Sciences of the United States of America, vol. 100, no. 7, pp. 3983–3988, 2003. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  10. M. Al-Hajj and M. F. Clarke, “Self-renewal and solid tumor stem cells,” Oncogene, vol. 23, no. 43, pp. 7274–7282, 2004. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  11. P. Dalerba, R. W. Cho, and M. F. Clarke, “Cancer stem cells: models and concepts,” Annual Review of Medicine, vol. 58, pp. 267–284, 2007. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  12. S. A. Mani, W. Guo, and W. Guo, “The epithelial-mesenchymal transition generates cells with properties of stem cells,” Cell, vol. 133, no. 4, pp. 704–715, 2008. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  13. C. J. Creighton, X. Li, and X. Li, “Residual breast cancers after conventional therapy display mesenchymal as well as tumor-initiating features,” Proceedings of the National Academy of Sciences of the United States of America, vol. 106, no. 33, pp. 13820–13825, 2009. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  14. E. D. Hay, “An overview of epithelio-mesenchymal transformation,” Acta Anatomica, vol. 154, no. 1, pp. 8–20, 1995. View at Scopus
  15. R. Kalluri and E. G. Neilson, “Epithelial-mesenchymal transition and its implications for fibrosis,” Journal of Clinical Investigation, vol. 112, no. 12, pp. 1776–1784, 2003. View at Publisher · View at Google Scholar · View at Scopus
  16. P. Damonte, J. P. Gregg, A. D. Borowsky, B. A. Keister, and R. D. Cardiff, “EMT tumorigenesis in the mouse mammary gland,” Laboratory Investigation, vol. 87, no. 12, pp. 1218–1226, 2007. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  17. M. Guarino, B. Rubino, and G. Ballabio, “The role of epithelial-mesenchymal transition in cancer pathology,” Pathology, vol. 39, no. 3, pp. 305–318, 2007. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  18. M. I. Kokkinos, R. Wafai, M. K. Wong, D. F. Newgreen, E. W. Thompson, and M. Waltham, “Vimentin and epithelial-mesenchymal transition in human breast cancer—observations in vitro and in vivo,” Cells Tissues Organs, vol. 185, no. 1–3, pp. 191–203, 2007. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  19. J. M. Lee, S. Dedhar, R. Kalluri, and E. W. Thompson, “The epithelial-mesenchymal transition: new insights in signaling, development, and disease,” Journal of Cell Biology, vol. 172, no. 7, pp. 973–981, 2006. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  20. D. Sarrió, S. M. Rodriguez-Pinilla, D. Hardisson, A. Cano, G. Moreno-Bueno, and J. Palacios, “Epithelial-mesenchymal transition in breast cancer relates to the basal-like phenotype,” Cancer Research, vol. 68, no. 4, pp. 989–997, 2008. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  21. A. J. Trimboli, K. Fukino, and K. Fukino, “Direct evidence for epithelial-mesenchymal transitions in breast cancer,” Cancer Research, vol. 68, no. 3, pp. 937–945, 2008. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  22. C. D. Stern, “Vertebrate gastrulation,” Current Opinion in Genetics and Development, vol. 2, no. 4, pp. 556–561, 1992. View at Scopus
  23. C. D. Stern, G. W. Ireland, S. E. Herrick, E. Gherardi, J. Gray, M. Perryman, and M. Stoker, “Epithelial scatter factor and development of the chick embryonic axis,” Development, vol. 110, no. 4, pp. 1271–1284, 1990. View at Scopus
  24. J. C. Pearson, D. Lemons, and W. McGinnis, “Modulating Hox gene functions during animal body patterning,” Nature Reviews Genetics, vol. 6, no. 12, pp. 893–904, 2005. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  25. T. Brabletz, A. Jung, S. Spaderna, F. Hlubek, and T. Kirchner, “Migrating cancer stem cells—an integrated concept of malignant tumour progression,” Nature Reviews Cancer, vol. 5, no. 9, pp. 744–749, 2005. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  26. J. P. Their, “Epithelial-mesenchymal transitions in tumor progression,” Nature Reviews Cancer, vol. 2, no. 6, pp. 442–454, 2002. View at Scopus
  27. A. Nawshad, D. LaGamba, and E. D. Hay, “Transforming growth factor β (TGFβ) signalling in palatal growth, apoptosis and epithelial mesenchymal transformation (EMT),” Archives of Oral Biology, vol. 49, no. 9, pp. 675–689, 2004. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  28. R. S. Muraoka-Cook, I. Shin, and I. Shin, “Activated type I TGFβ receptor kinase enhances the survival of mammary epithelial cells and accelerates tumor progression,” Oncogene, vol. 25, no. 24, pp. 3408–3423, 2006. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  29. J. J. Yin, K. Selander, and K. Selander, “TGF-β signaling blockade inhibits PTHrP secretion by breast cancer cells and bone metastases development,” Journal of Clinical Investigation, vol. 103, no. 2, pp. 197–206, 1999. View at Scopus
  30. N. Dumont and C. L. Arteaga, “Transforming growth factor-β and breast cancer: tumor promoting effects of transforming growth factor-β,” Breast Cancer Research, vol. 2, no. 2, pp. 125–132, 2000. View at Publisher · View at Google Scholar · View at Scopus
  31. S. Giampieri, C. Manning, S. Hooper, L. Jones, C. S. Hill, and E. Sahai, “Localized and reversible TGFβ signalling switches breast cancer cells from cohesive to single cell motility,” Nature Cell Biology, vol. 11, no. 11, pp. 1287–1296, 2009. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  32. E. A. Carver, R. Jiang, Y. Lan, K. F. Oram, and T. Gridley, “The mouse Snail gene encodes a key regulator of the epithelial-mesenchymal transition,” Molecular and Cellular Biology, vol. 21, no. 23, pp. 8184–8188, 2001. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  33. E. Rosivatz, I. Becker, and I. Becker, “Differential expression of the epithelial-mesenchymal transition regulators Snail, SIP1, and twist in gastric cancer,” American Journal of Pathology, vol. 161, no. 5, pp. 1881–1891, 2002. View at Scopus
  34. S. Vega, A. V. Morales, O. H. Ocaña, F. Valdés, I. Fabregat, and M. A. Nieto, “Snail blocks the cell cycle and confers resistance to cell death,” Genes and Development, vol. 18, no. 10, pp. 1131–1143, 2004. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  35. T. Hayashida, F. Takahashi, and F. Takahashi, “HOXB9, a gene overexpressed in breast cancer, promotes tumorigenicity and lung metastasis,” Proceedings of the National Academy of Sciences of the United States of America, vol. 107, no. 3, pp. 1100–1105, 2010. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  36. C. L. Chaffer, E. W. Thompson, and E. D. Williams, “Mesenchymal to epithelial transition in development and disease,” Cells Tissues Organs, vol. 185, no. 1-3, pp. 7–19, 2007. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  37. T. Tsuji, S. Ibaragi, and G. F. Hu, “Epithelial-mesenchymal transition and cell cooperativity in metastasis,” Cancer Research, vol. 69, no. 18, pp. 7135–7139, 2009. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  38. R. Li, J. Liang, and J. Liang, “A mesenchymal-to-epithelial transition initiates and is required for the nuclear reprogramming of mouse fibroblasts,” Cell Stem Cell, vol. 7, no. 1, pp. 51–63, 2010. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  39. J. P. Thiery, H. Acloque, R. Y. J. Huang, and M. A. Nieto, “Epithelial-mesenchymal transitions in development and disease,” Cell, vol. 139, no. 5, pp. 871–890, 2009. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  40. D. Bonnet and J. E. Dick, “Human acute myeloid leukemia is organized as a hierarchy that originates from a primitive hematopoietic cell,” Nature Medicine, vol. 3, no. 7, pp. 730–737, 1997. View at Publisher · View at Google Scholar · View at Scopus
  41. B. K. Abraham, P. Fritz, M. McClellan, P. Hauptvogel, M. Athelogou, and H. Brauch, “Prevalence of CD44+/CD24-/low cells in breast cancer may not be associated with clinical outcome but may favor distant metastasis,” Clinical Cancer Research, vol. 11, no. 3, pp. 1154–1159, 2005. View at Scopus
  42. R. Liu, X. Wang, and X. Wang, “The prognostic role of a gene signature from tumorigenic breast-cancer cells,” New England Journal of Medicine, vol. 356, no. 3, pp. 217–226, 2007. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  43. C. Sheridan, H. Kishimoto, and H. Kishimoto, “CD44+/CD24- breast cancer cells exhibit enhanced invase properties: an early step necessary for metastasis,” Breast Cancer Research, vol. 8, no. 5, article R59, 2006. View at Publisher · View at Google Scholar · View at PubMed
  44. M. Shipitsin, L. L. Campbell, and L. L. Campbell, “Molecular definition of breast tumor heterogeneity,” Cancer Cell, vol. 11, no. 3, pp. 259–273, 2007. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  45. C. Ginestier, M. H. Hur, and M. H. Hur, “ALDH1 is a marker of normal and malignant human mammary stem cells and a predictor of poor clinical outcome,” Cell Stem Cell, vol. 1, no. 5, pp. 555–567, 2007. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  46. E. Charafe-Jauffret, C. Ginestier, and C. Ginestier, “Aldehyde dehydrogenase 1-positive cancer stem cells mediate metastasis and poor clinical outcome in inflammatory breast cancer,” Clinical Cancer Research, vol. 16, no. 1, pp. 45–55, 2010. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  47. Y. Su, Q. Qiu, and Q. Qiu, “Aldehyde dehydrogenase 1 A1-positive cell population is enriched in tumor-initiating cells and associated with progression of bladder cancer,” Cancer Epidemiology Biomarkers and Prevention, vol. 19, no. 2, pp. 327–337, 2010. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  48. J. Feng, Q. Qi, and Q. Qi, “Aldehyde dehydrogenase 1 is a tumor stem cell-associated marker in lung cancer,” Molecular Cancer Research, vol. 7, no. 3, pp. 330–338, 2009. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  49. N. Barker, J. H. van Es, and J. H. van Es, “Identification of stem cells in small intestine and colon by marker gene Lgr5,” Nature, vol. 449, no. 7165, pp. 1003–1007, 2007. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  50. N. Barker, R. A. Ridgway, and R. A. Ridgway, “Crypt stem cells as the cells-of-origin of intestinal cancer,” Nature, vol. 457, no. 7229, pp. 608–611, 2009. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  51. H. Uchida, K. Yamazaki, and K. Yamazaki, “Overexpression of leucine-rich repeat-containing G protein-coupled receptor 5 in colorectal cancer,” Cancer Science, vol. 101, no. 7, pp. 1731–1737, 2010. View at Publisher · View at Google Scholar · View at PubMed
  52. J. Massagué, “TGFβ in cancer,” Cell, vol. 134, no. 2, pp. 215–230, 2008. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  53. M. A. Huber, H. Beug, and T. Wirth, “Epithelial-mesenchymal transition: NF-κB takes center stage,” Cell Cycle, vol. 3, no. 12, pp. 1477–1480, 2004. View at Scopus
  54. J. H. Taube, J. I. Herschkowitz, and J. I. Herschkowitz, “Core epithelial-to-mesenchymal transition interactome gene-expression signature is associated with claudin-low and metaplastic breast cancer subtypes,” Proceedings of the National Academy of Sciences of the United States of America, vol. 107, no. 35, pp. 15449–15454, 2010. View at Publisher · View at Google Scholar · View at PubMed
  55. J. Fuxe, T. Vincent, and A. G. de Herreros, “Transcriptional crosstalk between TGFβ and stem cell pathways in tumor cell invasion: role of EMT promoting Smad complexes,” Cell Cycle, vol. 9, no. 12, pp. 2363–2374, 2010. View at Publisher · View at Google Scholar
  56. J. Deka, N. Wiedemann, and N. Wiedemann, “Bcl9/Bcl9l are critical for Wnt-mediated regulation of stem cell traits in colon epithelium and adenocarcinomas,” Cancer Research, vol. 70, no. 16, pp. 6619–6628, 2010. View at Publisher · View at Google Scholar · View at PubMed
  57. I. Malanchi, H. Peinado, and H. Peinado, “Cutaneous cancer stem cell maintenance is dependent on β-catenin signalling,” Nature, vol. 452, no. 7187, pp. 650–653, 2008. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  58. P. Neth, C. Ries, M. Karow, V. Egea, M. Ilmer, and M. Jochum, “The Wnt signal transduction pathway in stem cells and cancer cells: influence on cellular invasion,” Stem Cell Reviews, vol. 3, no. 1, pp. 18–29, 2007. View at Publisher · View at Google Scholar · View at Scopus
  59. B. Tang, N. Yoo, and N. Yoo, “Transforming growth factor-β can suppress tumorigenesis through effects on the putative cancer stem or early progenitor cell and committed progeny in a breast cancer xenograft model,” Cancer Research, vol. 67, no. 18, pp. 8643–8652, 2007. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  60. C. Alix-Panabières, S. Riethdorf, and K. Pantel, “Circulating tumor cells and bone marrow micrometastasis,” Clinical Cancer Research, vol. 14, no. 16, pp. 5013–5021, 2008. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  61. R. Bernards and R. A. Weinberg, “A progression puzzle,” Nature, vol. 418, no. 6900, p. 823, 2002. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  62. S. Nagrath, L. V. Sequist, and L. V. Sequist, “Isolation of rare circulating tumour cells in cancer patients by microchip technology,” Nature, vol. 450, no. 7173, pp. 1235–1239, 2007. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  63. M. Tewes, B. Aktas, A. Welt, S. Mueller, S. Hauch, R. Kimmig, and S. Kasimir-Bauer, “Molecular profiling and predictive value of circulating tumor cells in patients with metastatic breast cancer: an option for monitoring response to breast cancer related therapies,” Breast Cancer Research and Treatment, vol. 115, no. 3, pp. 581–590, 2009. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  64. S. Maheswaran, L. V. Sequist, and L. V. Sequist, “Detection of mutations in EGFR in circulating lung-cancer cells,” New England Journal of Medicine, vol. 359, no. 4, pp. 366–377, 2008. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  65. B. Aktas, M. Tewes, T. Fehm, S. Hauch, R. Kimmig, and S. Kasimir-Bauer, “Stem cell and epithelial-mesenchymal transition markers are frequently overexpressed in circulating tumor cells of metastatic breast cancer patients,” Breast Cancer Research, vol. 11, no. 4, p. R46, 2009. View at Scopus
  66. K. Pantel, G. Schlimok, and G. Schlimok, “Methodological analysis of immunocytochemical screening for disseminated epithelial tumor cells in bone marrow,” Journal of Hematotherapy, vol. 3, no. 3, pp. 165–173, 1994. View at Scopus
  67. M. A. Watson, L. R. Ylagan, and L. R. Ylagan, “Isolation and molecular profiling of bone marrow micrometastases identifies TWIST1 as a marker of early tumor relapse in breast cancer patients,” Clinical Cancer Research, vol. 13, no. 17, pp. 5001–5009, 2007. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  68. J. Domen, K. L. Gandy, and I. L. Weissman, “Systemic overexpression of BCL-2 in the hematopoietic system protects transgenic mice from the consequences of lethal irradiation,” Blood, vol. 91, no. 7, pp. 2272–2282, 1998. View at Scopus
  69. R. Peters, S. Leyvraz, and L. Perey, “Apoptotic regulation in primitive hematopoietic precursors,” Blood, vol. 92, no. 6, pp. 2041–2052, 1998. View at Scopus
  70. L. Austin Doyle, W. Yang, L. V. Abruzzo, T. Krogmann, Y. Gao, A. K. Rishi, and D. D. Ross, “A multidrug resistance transporter from human MCF-7 breast cancer cells,” Proceedings of the National Academy of Sciences of the United States of America, vol. 95, no. 26, pp. 15665–15670, 1998. View at Publisher · View at Google Scholar · View at Scopus
  71. N. Haraguchi, T. Utsunomiya, H. Inoue, F. Tanaka, K. Mimori, G. F. Barnard, and M. Mori, “Characterization of a side population of cancer cells from human gastrointestinal system,” Stem Cells, vol. 24, no. 3, pp. 506–513, 2006. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  72. K. Miyake, L. Mickley, and L. Mickley, “Molecular cloning of cDNAs which are highly overexpressed in mitoxantrone-resistant cells: demonstration of homology to ABC transport genes,” Cancer Research, vol. 59, no. 1, pp. 8–13, 1999. View at Scopus
  73. C. Hirschmann-Jax, A. E. Foster, and A. E. Foster, “A distinct "side population" of cells with high drug efflux capacity in human tumor cells,” Proceedings of the National Academy of Sciences of the United States of America, vol. 101, no. 39, pp. 14228–14233, 2004. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  74. S. Kawabata, M. Oka, and M. Oka, “Expression and functional analyses of breast cancer resistance protein in lung cancer,” Clinical Cancer Research, vol. 9, no. 8, pp. 3052–3057, 2003. View at Scopus
  75. K. Fukuda, Y. Saikawa, and Y. Saikawa, “Tumor initiating potential of side population cells in human gastric cancer,” International Journal of Oncology, vol. 34, no. 5, pp. 1201–1207, 2009. View at Publisher · View at Google Scholar · View at Scopus
  76. G. Z. Cheng, J. Chan, Q. Wang, W. Zhang, C. D. Sun, and L. H. Wang, “Twist transcriptionally up-regulates AKT2 in breast cancer cells leading to increased migration, invasion, and resistance to paclitaxel,” Cancer Research, vol. 67, no. 5, pp. 1979–1987, 2007. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  77. A. D. Yang, F. Fan, and F. Fan, “Chronic oxaliplatin resistance induces epithelial-to-mesenchymal transition in colorectal cancer cell lines,” Clinical Cancer Research, vol. 12, no. 14, pp. 4147–4153, 2006. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  78. H. Kajiyama, K. Shibata, M. Terauchi, M. Yamashita, K. Ino, A. Nawa, and F. Kikkawa, “Chemoresistance to paclitaxel induces epithelial-mesenchymal transition and enhances metastatic potential for epithelial ovarian carcinoma cells,” International Journal of Oncology, vol. 31, no. 2, pp. 277–283, 2007. View at Scopus
  79. S. Thomson, E. Buck, and E. Buck, “Epithelial to mesenchymal transition is a determinant of sensitivity of non-small-cell lung carcinoma cell lines and xenografts to epidermal growth factor receptor inhibition,” Cancer Research, vol. 65, no. 20, pp. 9455–9462, 2005. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  80. X. Li, M. T. Lewis, and M. T. Lewis, “Intrinsic resistance of tumorigenic breast cancer cells to chemotherapy,” Journal of the National Cancer Institute, vol. 100, no. 9, pp. 672–679, 2008. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  81. P. B. Gupta, T. T. Onder, G. Jiang, K. Tao, C. Kuperwasser, R. A. Weinberg, and E. S. Lander, “Identification of selective inhibitors of cancer stem cells by high-throughput screening,” Cell, vol. 138, no. 4, pp. 645–659, 2009. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus