Epithelial-mesenchymal plasticity of breast cancer stem cells: Implications for metastasis and therapeutic resistance

Current Pharmaceutical Design

Volumn 21, Issue 10, 2015, Pages 1301-1310

  Luo, Ming ^a   Brooks, Michael ^a   Wicha, Max S ^a  

^a UNIVERSITY OF MICHIGAN COMPREHENSIVE CANCER CENTER   (United States)

Author keywords

Breast cancer stem cells; EMT; MET; Metastasis; Therapeutic resistance

Indexed keywords

CYCLOPHOSPHAMIDE; DOCETAXEL; DOXORUBICIN; EPIRUBICIN; LAPATINIB; PACLITAXEL; TRASTUZUMAB; UVOMORULIN; VIMENTIN; ANTINEOPLASTIC AGENT;

ARTICLE; BREAST CANCER; BREAST CARCINOGENESIS; BREAST EPITHELIUM CELL; BREAST METASTASIS; CANCER ADJUVANT THERAPY; CANCER CELL; CANCER GROWTH; CANCER PROGNOSIS; CANCER RADIOTHERAPY; CANCER RESISTANCE; CANCER STEM CELL; CARCINOGENICITY; CELL INVASION; DISTANT METASTASIS; EPITHELIAL MESENCHYMAL TRANSITION; HUMAN; IONIZING RADIATION; METASTASIS; MICROMETASTASIS; NONHUMAN; PLASTICITY; PRIORITY JOURNAL; TUMOR INVASION; TUMOR MICROENVIRONMENT; ANIMAL; BREAST NEOPLASMS; DRUG EFFECTS; DRUG RESISTANCE; FEMALE; METABOLISM; PATHOLOGY; PHYSIOLOGY;

ANIMALS; ANTINEOPLASTIC AGENTS; BREAST NEOPLASMS; DRUG RESISTANCE, NEOPLASM; EPITHELIAL-MESENCHYMAL TRANSITION; FEMALE; HUMANS; NEOPLASTIC STEM CELLS;

EID: 84926319631     PISSN: 13816128     EISSN: 18734286     Source Type: Journal    
DOI: 10.2174/1381612821666141211120604     Document Type: Article

References (124)

1. Servick K. Breast cancer. Breast cancer: a world of differences. Science 2014; 343(6178): 1452-3.
2. Wicha MS, Liu S, Dontu G. Cancer stem cells: an old idea--a paradigm shift. Cancer Res 2006; 66(4): 1883-90; discussion 95-6.
3. Liu S, Wicha MS. Targeting breast cancer stem cells. J clinical oncology : official J the American Society of Clinical Oncology 2010; 28(25): 4006-12.
4. Charafe-Jauffret E, Monville F, Ginestier C, Dontu G, Birnbaum D, Wicha MS. Cancer stem cells in breast: current opinion and future challenges. Pathobiology : J Immunopathol, Mol Cellular Biol 2008; 75(2): 75-84.
5. Al-Hajj M, Wicha MS, Benito-Hernandez A, Morrison SJ, Clarke MF. Prospective identification of tumorigenic breast cancer cells. Proc Natl Acad Sci USA 2003; 100(7): 3983-8.
6. Ginestier C, Hur MH, Charafe-Jauffret E, et al. ALDH1 is a marker of normal and malignant human mammary stem cells and a predictor of poor clinical outcome. Cell stem cell 2007; 1(5): 555-67.
7. Liu S, Cong Y, Wang D, et al. Breast Cancer Stem Cells Transition between Epithelial and Mesenchymal States Reflective of their Normal Counterparts. Stem Cell Reports 2014; 2(1): 78-91.
8. Nieto MA. Epithelial plasticity: a common theme in embryonic and cancer cells. Science 2013; 342(6159): 1234850.
9. Thiery JP. Epithelial-mesenchymal transitions in tumour progression. Nature Rev Cancer 2002; 2(6): 442-54.
10. Lee JM, Dedhar S, Kalluri R, Thompson EW. The epithelialmesenchymal transition: new insights in signaling, development, and disease. J cell biology 2006; 172(7): 973-81.
11. Hugo H, Ackland ML, Blick T, et al. Epithelial--mesenchymal and mesenchymal--epithelial transitions in carcinoma progression. J Cellular Physiol 2007; 213(2): 374-83.
12. Thiery JP, Sleeman JP. Complex networks orchestrate epithelialmesenchymal transitions. Nature Rev Mol Cell Biol 2006; 7(2): 131-42.
13. Peinado H, Olmeda D, Cano A. Snail, Zeb and bHLH factors in tumour progression: an alliance against the epithelial phenotype? Nat Rev Cancer 2007; 7(6): 415-28.
14. Moreno-Bueno G, Portillo F, Cano A. Transcriptional regulation of cell polarity in EMT and cancer. Oncogene 2008; 27(55): 6958-69.
15. Brabletz T. To differentiate or not--routes towards metastasis. Nat Rev Cancer 2012; 12(6): 425-36.
16. Kalluri R, Weinberg RA. The basics of epithelial-mesenchymal transition. J Clin Investigation 2009; 119(6): 1420-8.
17. Balic M, Lin H, Young L, et al. Most early disseminated cancer cells detected in bone marrow of breast cancer patients have a putative breast cancer stem cell phenotype. Clinical cancer research : an official J Am Assoc Cancer Res 2006; 12(19): 5615-21.
18. Watson MA, Ylagan LR, Trinkaus KM, Gillanders WE, Naughton MJ, Weilbaecher KN, et al. Isolation and molecular profiling of bone marrow micrometastases identifies TWIST1 as a marker of early tumor relapse in breast cancer patients. Clinical cancer research : an official J Am Assoc Cancer Res 2007; 13(17): 5001-9.
19. Raimondi C, Gradilone A, Naso G, et al. Epithelial-mesenchymal transition and stemness features in circulating tumor cells from breast cancer patients. Breast Cancer Res Treatment 2011; 130(2): 449-55.
20. Pantel K, Alix-Panabieres C, Riethdorf S. Cancer micrometastases. Nat Rev Clin Oncol 2009; 6(6): 339-51.
21. Yu M, Stott S, Toner M, Maheswaran S, Haber DA. Circulating tumor cells: approaches to isolation and characterization. J Cell Biol 2011; 192(3): 373-82.
22. Cristofanilli M, Budd GT, Ellis MJ, et al. Circulating tumor cells, disease progression, and survival in metastatic breast cancer. N Eng J Med 2004; 351(8): 781-91.
23. Budd GT, Cristofanilli M, Ellis MJ, et al. Circulating tumor cells versus imaging--predicting overall survival in metastatic breast cancer. Clinical cancer research : an official J Am Assoc Cancer Res 2006; 12(21): 6403-9.
24. Baccelli I, Schneeweiss A, Riethdorf S, et al. Identification of a population of blood circulating tumor cells from breast cancer patients that initiates metastasis in a xenograft assay. Nat Biotechnol 2013; 31(6): 539-44.
25. Yu M, Bardia A, Wittner BS, et al. Circulating breast tumor cells exhibit dynamic changes in epithelial and mesenchymal composition. Science 2013; 339(6119): 580-4.
26. Shipitsin M, Campbell LL, Argani P, et al. Molecular definition of breast tumor heterogeneity. Cancer Cell 2007; 11(3): 259-73.
27. Malanchi I, Santamaria-Martinez A, Susanto E, et al. Interactions between cancer stem cells and their niche govern metastatic colonization. Nature 2012; 481(7379): 85-9.
28. Tsai JH, Donaher JL, Murphy DA, Chau S, Yang J. Spatiotemporal regulation of epithelial-mesenchymal transition is essential for squamous cell carcinoma metastasis. Cancer Cell 2012; 22(6): 725-36.
29. Ocana OH, Corcoles R, Fabra A, et al. Metastatic colonization requires the repression of the epithelial-mesenchymal transition inducer Prrx1. Cancer Cell 2012; 22(6): 709-24.
30. Korpal M, Ell BJ, Buffa FM, et al. Direct targeting of Sec23a by miR-200s influences cancer cell secretome and promotes metastatic colonization. Nature Med 2011; 17(9): 1101-8.
31. Stankic M, Pavlovic S, Chin Y, et al. TGF-beta-Id1 Signaling Opposes Twist1 and Promotes Metastatic Colonization via a Mesenchymal-to-Epithelial Transition. Cell reports 2013; 5(5): 1228-42.
32. Cameron MD, Schmidt EE, Kerkvliet N, et al. Temporal progression of metastasis in lung: cell survival, dormancy, and location dependence of metastatic inefficiency. Cancer Res 2000; 60(9): 2541-6.
33. Chambers AF, Naumov GN, Varghese HJ, Nadkarni KV, Mac-Donald IC, Groom AC. Critical steps in hematogenous metastasis: an overview. Surgical Oncol Clin North America 2001; 10(2): 243-55.
34. Chambers AF, Groom AC, MacDonald IC. Dissemination and growth of cancer cells in metastatic sites. Nat Rev Cancer 2002; 2(8): 563-72.
35. Fidler IJ. The pathogenesis of cancer metastasis: the 'seed and soil' hypothesis revisited. Nat Rev Cancer 2003; 3(6): 453-8.
36. Gupta GP, Massague J. Cancer metastasis: building a framework. Cell 2006; 127(4): 679-95.
37. Liu R, Wang X, Chen GY, et al. The prognostic role of a gene signature from tumorigenic breast-cancer cells. N Eng J Med 2007; 356(3): 217-26.
38. Liu H, Patel MR, Prescher JA, et al. Cancer stem cells from human breast tumors are involved in spontaneous metastases in orthotopic mouse models. Proc Natl Acad Sci USA 2010; 107(42): 18115-20.
39. Patel SA, Ramkissoon SH, Bryan M, et al. Delineation of breast cancer cell hierarchy identifies the subset responsible for dormancy. Scientific Reports 2012; 2: 906.
40. Lagadec C, Vlashi E, Della Donna L, et al. Survival and selfrenewing capacity of breast cancer initiating cells during fractionated radiation treatment. Breast cancer research : BCR 2010; 12(1): R13.
41. Phillips TM, McBride WH, Pajonk F. The response of CD24(-/low)/CD44+ breast cancer-initiating cells to radiation. J Natl Cancer Institute 2006; 98(24): 1777-85.
42. Karimi-Busheri F, Rasouli-Nia A, Mackey JR, Weinfeld M. Senescence evasion by MCF-7 human breast tumor-initiating cells. Breast Cancer Research : BCR 2010; 12(3): R31.
43. Fillmore CM, Kuperwasser C. Human breast cancer cell lines contain stem-like cells that self-renew, give rise to phenotypically diverse progeny and survive chemotherapy. Breast Cancer Research : BCR 2008; 10(2): R25.
44. Shafee N, Smith CR, Wei S, et al. Cancer stem cells contribute to cisplatin resistance in Brca1/p53-mediated mouse mammary tumors. Cancer Res 2008; 68(9): 3243-50.
45. Woodward WA, Chen MS, Behbod F, Alfaro MP, Buchholz TA, Rosen JM. WNT/beta-catenin mediates radiation resistance of mouse mammary progenitor cells. Proc Natl Acad Sci USA 2007; 104(2): 618-23.
46. Diehn M, Cho RW, Lobo NA, et al. Association of reactive oxygen species levels and radioresistance in cancer stem cells. Nature 2009; 458(7239): 780-3.
47. Yu F, Yao H, Zhu P, et al. let-7 regulates self renewal and tumorigenicity of breast cancer cells. Cell 2007; 131(6): 1109-23.
48. Zielske SP, Spalding AC, Wicha MS, Lawrence TS. Ablation of breast cancer stem cells with radiation. Translational Oncol 2011; 4(4): 227-33.
49. Li X, Lewis MT, Huang J, et al. Intrinsic resistance of tumorigenic breast cancer cells to chemotherapy. J Natl Cancer Institute 2008; 100(9): 672-9.
50. Korkaya H, Paulson A, Iovino F, Wicha MS. HER2 regulates the mammary stem/progenitor cell population driving tumorigenesis and invasion. Oncogene 2008; 27(47): 6120-30.
51. Tanei T, Morimoto K, Shimazu K, et al. Association of breast cancer stem cells identified by aldehyde dehydrogenase 1 expression with resistance to sequential Paclitaxel and epirubicin-based chemotherapy for breast cancers. Clinical cancer research : an official J Am Assoc Cancer Res 2009; 15(12): 4234-41.
52. Alamgeer M, Ganju F, Kumar B, Fox J, Hart S, White M, Harris M, Stuckey J, Prodanovic Z, Schneider-Kolsky ME and Watkins DN. Changes in aldehyde dehydrogenase-1 expression during neoadjuvant chemotherapy predict outcome in locally advanced breast cancer. Breast Cancer Res 2014; 16: R44.
53. Liu S, Ginestier C, Ou SJ, et al. Breast cancer stem cells are regulated by mesenchymal stem cells through cytokine networks. Cancer Res 2011; 71(2): 614-24.
54. Moreb JS, Maccow C, Schweder M, Hecomovich J. Expression of antisense RNA to aldehyde dehydrogenase class-1 sensitizes tumor cells to 4-hydroperoxycyclophosphamide in vitro. J Pharmacol Experimental Therapeutics 2000; 293(2): 390-6.
55. Magni M, Shammah S, Schiro R, Mellado W, Dalla-Favera R, Gianni AM. Induction of cyclophosphamide-resistance by aldehyde-dehydrogenase gene transfer. Blood 1996; 87(3): 1097-103.
56. Hirschmann-Jax C, Foster AE, Wulf GG, et al. A distinct "side population" of cells with high drug efflux capacity in human tumor cells. Proc Natl Acad Sci USA 2004; 101(39): 14228-33.
57. Patrawala L, Calhoun T, Schneider-Broussard R, Zhou J, Claypool K, Tang DG. Side population is enriched in tumorigenic, stem-like cancer cells, whereas ABCG2+ and ABCG2-cancer cells are similarly tumorigenic. Cancer Res 2005; 65(14): 6207-19.
58. Britton KM, Eyre R, Harvey IJ, et al. Breast cancer, side population cells and ABCG2 expression. Cancer Letters 2012; 323(1): 97-105.
59. Nakanishi T, Chumsri S, Khakpour N, et al. Side-population cells in luminal-type breast cancer have tumour-initiating cell properties, and are regulated by HER2 expression and signalling. Br J Cancer 2010; 102(5): 815-26.
60. Yin H, Glass J. The phenotypic radiation resistance of CD44+/CD24(-or low) breast cancer cells is mediated through the enhanced activation of ATM signaling. PloS one 2011; 6(9): e24080.
61. Zhang M, Atkinson RL, Rosen JM. Selective targeting of radiationresistant tumor-initiating cells. Proc Natl Acad Sci USA 2010; 107(8): 3522-7.
62. Sheridan C, Kishimoto H, Fuchs RK, et al. CD44+/CD24-breast cancer cells exhibit enhanced invasive properties: an early step necessary for metastasis. Breast Cancer Res : BCR 2006; 8(5): R59.
63. Ponta H, Sherman L, Herrlich PA. CD44: from adhesion molecules to signalling regulators. Nat Rev Mol Cell Biol 2003; 4(1): 33-45.
64. Cheng C, Yaffe MB, Sharp PA. A positive feedback loop couples Ras activation and CD44 alternative splicing. Genes Development 2006; 20(13): 1715-20.
65. Orian-Rousseau V, Chen L, Sleeman JP, Herrlich P, Ponta H. CD44 is required for two consecutive steps in HGF/c-Met signaling. Genes Development 2002; 16(23): 3074-86.
66. Sherman LS, Rizvi TA, Karyala S, Ratner N. CD44 enhances neuregulin signaling by Schwann cells. J Cell Biol 2000; 150(5): 1071-84.
67. Bourguignon LY, Zhu H, Chu A, Iida N, Zhang L, Hung MC. Interaction between the adhesion receptor, CD44, and the oncogene product, p185HER2, promotes human ovarian tumor cell activation. J Biological Chem 1997; 272(44): 27913-8.
68. Draffin JE, McFarlane S, Hill A, Johnston PG, Waugh DJ. CD44 potentiates the adherence of metastatic prostate and breast cancer cells to bone marrow endothelial cells. Cancer Res 2004; 64(16): 5702-11.
69. Hiraga T, Ito S, Nakamura H. Cancer stem-like cell marker CD44 promotes bone metastases by enhancing tumorigenicity, cell motility, and hyaluronan production. Cancer Res 2013; 73(13): 4112-22.
70. Brown RL, Reinke LM, Damerow MS, et al. CD44 splice isoform switching in human and mouse epithelium is essential for epithelial-mesenchymal transition and breast cancer progression. J Clin Investigation 2011; 121(3): 1064-74.
71. Mani SA, Guo W, Liao MJ, et al. The epithelial-mesenchymal transition generates cells with properties of stem cells. Cell 2008; 133(4): 704-15.
72. Sigurdsson V, Hilmarsdottir B, Sigmundsdottir H, et al. Endothelial induced EMT in breast epithelial cells with stem cell properties. PloS one 2011; 6(9): e23833.
73. Guo W, Keckesova Z, Donaher JL, et al. Slug and Sox9 cooperatively determine the mammary stem cell state. Cell 2012; 148(5): 1015-28.
74. Lindeman GJ, Visvader JE. Insights into the cell of origin in breast cancer and breast cancer stem cells. Asia-Pacific J Clin Oncol 2010; 6(2): 89-97.
75. Lim E, Vaillant F, Wu D, et al. Aberrant luminal progenitors as the candidate target population for basal tumor development in BRCA1 mutation carriers. Nature Med 2009; 15(8): 907-13.
76. Visvader JE. Keeping abreast of the mammary epithelial hierarchy and breast tumorigenesis. Genes Development 2009; 23(22): 2563-77.
77. Calabrese C, Poppleton H, Kocak M, et al. A perivascular niche for brain tumor stem cells. Cancer Cell 2007; 11(1): 69-82.
78. Zhang Z, Dong Z, Lauxen IS, Filho MS, Nor JE. Endothelial Cell-Secreted EGF Induces Epithelial to Mesenchymal Transition and Endows Head and Neck Cancer Cells with Stem-like Phenotype. Cancer Res 2014; 74(10): 2869-81.
79. Merrilees MJ, Sodek J. Synthesis of TGF-beta 1 by vascular endothelial cells is correlated with cell spreading. J Vascular Res 1992; 29(5): 376-84.
80. Xu J, Lamouille S, Derynck R. TGF-beta-induced epithelial to mesenchymal transition. Cell Res 2009; 19(2): 156-72.
81. Guo X, Oshima H, Kitmura T, Taketo MM, Oshima M. Stromal fibroblasts activated by tumor cells promote angiogenesis in mouse gastric cancer. J Biological Chem 2008; 283(28): 19864-71.
82. Orimo A, Weinberg RA. Stromal fibroblasts in cancer: a novel tumor-promoting cell type. Cell Cycle 2006; 5(15): 1597-601.
83. Tyan SW, Kuo WH, Huang CK, et al. Breast cancer cells induce cancer-associated fibroblasts to secrete hepatocyte growth factor to enhance breast tumorigenesis. PloS one 2011; 6(1): e15313.
84. Stern R, Shuster S, Neudecker BA, Formby B. Lactate stimulates fibroblast expression of hyaluronan and CD44: the Warburg effect revisited. Experimental cell Res 2002; 276(1): 24-31.
85. Orimo A, Gupta PB, Sgroi DC, et al. Stromal fibroblasts present in invasive human breast carcinomas promote tumor growth and angiogenesis through elevated SDF-1/CXCL12 secretion. Cell 2005; 121(3): 335-48.
86. Yu Y, Xiao C, Tan L, Wang Q, Li X, Feng Y. Cancer-associated fibroblasts induce epithelial-mesenchymal transition of breast cancer cells through paracrine TGF-_signalling. British J cancer 2013.
87. Zhou Y, Kim J, Yuan X, Braun T. Epigenetic modifications of stem cells: a paradigm for the control of cardiac progenitor cells. Circulation Res 2011; 109(9): 1067-81.
88. Lund AH, van Lohuizen M. Epigenetics and cancer. Genes Development 2004; 18(19): 2315-35.
89. Herceg Z, Vaissiere T. Epigenetic mechanisms and cancer: an interface between the environment and the genome. (1559-2308 (Electronic)).
90. Chaffer Christine L, Marjanovic Nemanja D, Lee T, et al. Poised Chromatin at the ZEB1 Promoter Enables Breast Cancer Cell Plasticity and Enhances Tumorigenicity. Cell 154(1): 61-74.
91. Suva ML, Riggi N, Janiszewska M, et al. EZH2 is essential for glioblastoma cancer stem cell maintenance. Cancer Res 2009; 69(24): 9211-8.
92. Jene-Sanz A, Varaljai R, Vilkova AV, et al. Expression of polycomb targets predicts breast cancer prognosis. Mol Cellular Biol 2013; 33(19): 3951-61.
93. Cao Q, Yu J, Dhanasekaran SM, et al. Repression of E-cadherin by the polycomb group protein EZH2 in cancer. Oncogene 2008; 27(58): 7274-84.
94. Iliopoulos D, Lindahl-Allen M, Polytarchou C, Hirsch HA, Tsichlis PN, Struhl K. Loss of miR-200 inhibition of Suz12 leads to polycomb-mediated repression required for the formation and maintenance of cancer stem cells. Molecular Cell 2010; 39(5): 761-72.
95. Prat A, Parker JS, Karginova O, et al. Phenotypic and molecular characterization of the claudin-low intrinsic subtype of breast cancer. Breast cancer research : BCR 2010; 12(5): R68.
96. Morel AP, Lievre M, Thomas C, Hinkal G, Ansieau S, Puisieux A. Generation of breast cancer stem cells through epithelialmesenchymal transition. PloS one 2008; 3(8): e2888.
97. Celia-Terrassa T, Meca-Cortes O, Mateo F, et al. Epithelialmesenchymal transition can suppress major attributes of human epithelial tumor-initiating cells. J Clin Investigation 2012; 122(5): 1849-68.
98. Liu S, Clouthier SG, Wicha MS. Role of microRNAs in the regulation of breast cancer stem cells. J Mammary Gland Biol Neoplasia 2012; 17(1): 15-21.
99. Creighton CJ, Li X, Landis M, et al. Residual breast cancers after conventional therapy display mesenchymal as well as tumorinitiating features. Proc Natl Acad Sci USA 2009; 106(33): 13820-5.
100. [100] Chang JC, Wooten EC, Tsimelzon A, et al. Patterns of resistance and incomplete response to docetaxel by gene expression profiling in breast cancer patients. J clinical oncology: official J Am Soc Clin Oncol 2005; 23(6): 1169-77.
101. [101] Lim E, Vaillant F, Wu D, et al. Aberrant luminal progenitors as the candidate target population for basal tumor development in BRCA1 mutation carriers. Nat Med 2009; 15(8): 907-13.
102. [102] Molyneux G, Geyer FC, Magnay FA, et al. BRCA1 basal-like breast cancers originate from luminal epithelial progenitors and not from basal stem cells. Cell stem cell 2010; 7(3): 403-17.
103. [103] Proia TA, Keller PJ, Gupta PB, et al. Genetic predisposition directs breast cancer phenotype by dictating progenitor cell fate. Cell stem cell 2011; 8(2): 149-63.
104. [104] Keller PJ, Arendt LM, Skibinski A, et al. Defining the cellular precursors to human breast cancer. Proc Natl Acad Sci USA 2012; 109(8): 2772-7.
105. [105] Van Keymeulen A, Rocha AS, Ousset M, et al. Distinct stem cells contribute to mammary gland development and maintenance. Nature 2011; 479(7372): 189-93.
106. [106] Liu S, Ginestier C, Charafe-Jauffret E, et al. BRCA1 regulates human mammary stem/progenitor cell fate. Proc Natl Acad Sci USA 2008; 105(5): 1680-5.
107. [107] Chaffer CL, Brueckmann I, Scheel C, et al. Normal and neoplastic nonstem cells can spontaneously convert to a stem-like state. Proc Natl Acad Sci USA 2011; 108(19): 7950-5.
108. [108] Chaffer CL, Marjanovic ND, Lee T, et al. Poised chromatin at the ZEB1 promoter enables breast cancer cell plasticity and enhances tumorigenicity. Cell 2013; 154(1): 61-74.
109. [109] Tsai JH, Yang J. Epithelial-mesenchymal plasticity in carcinoma metastasis. Genes Development 2013; 27(20): 2192-206.
110. [110] Reka AK, Kuick R, Kurapati H, Standiford TJ, Omenn GS, Keshamouni VG. Identifying inhibitors of epithelial-mesenchymal transition by connectivity map-based systems approach. J thoracic oncology : official publication of the International Association for the Study of Lung Cancer 2011; 6(11): 1784-92.
111. [111] Chua KN, Sim WJ, Racine V, Lee SY, Goh BC, Thiery JP. A cellbased small molecule screening method for identifying inhibitors of epithelial-mesenchymal transition in carcinoma. PloS one 2012; 7(3): e33183.
112. [112] Angelucci A, Gravina GL, Rucci N, et al. Suppression of EGF-R signaling reduces the incidence of prostate cancer metastasis in nude mice. Endocrine-related Cancer 2006; 13(1): 197-210.
113. [113] Lo HW, Hsu SC, Xia W, et al. Epidermal growth factor receptor cooperates with signal transducer and activator of transcription 3 to induce epithelial-mesenchymal transition in cancer cells via upregulation of TWIST gene expression. Cancer Res 2007; 67(19): 9066-76.
114. [114] Kim HJ, Litzenburger BC, Cui X, et al. Constitutively active type I insulin-like growth factor receptor causes transformation and xenograft growth of immortalized mammary epithelial cells and is accompanied by an epithelial-to-mesenchymal transition mediated by NF-kappaB and snail. Mol and Cellular Biol 2007; 27(8): 3165-75.
115. [115] Thomson S, Buck E, Petti F, et al. 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 Res 2005; 65(20): 9455-62.
116. [116] Fuchs BC, Fujii T, Dorfman JD, et al. Epithelial-to-mesenchymal transition and integrin-linked kinase mediate sensitivity to epidermal growth factor receptor inhibition in human hepatoma cells. Cancer Res 2008; 68(7): 2391-9.
117. [117] Frederick BA, Helfrich BA, Coldren CD, et al. Epithelial to mesenchymal transition predicts gefitinib resistance in cell lines of head and neck squamous cell carcinoma and non-small cell lung carcinoma. Mol Cancer Therapeutics 2007; 6(6): 1683-91.
118. [118] Buck E, Eyzaguirre A, Rosenfeld-Franklin M, et al. Feedback mechanisms promote cooperativity for small molecule inhibitors of epidermal and insulin-like growth factor receptors. Cancer Res 2008; 68(20): 8322-32.
119. [119] Thomson S, Petti F, Sujka-Kwok I, et al. A systems view of epithelial-mesenchymal transition signaling states. Clin Experimental Metastasis 2011; 28(2): 137-55.
120. [120] Korkaya H, Liu S, Wicha MS. Regulation of cancer stem cells by cytokine networks: attacking cancer's inflammatory roots. Clinical cancer research : an official J Am Assoc Cancer Res 2011; 17(19): 6125-9.
121. [121] Sansone P, Storci G, Tavolari S, et al. IL-6 triggers malignant features in mammospheres from human ductal breast carcinoma and normal mammary gland. J Clin Invest 2007; 117(12): 3988-4002.
122. [122] Korkaya H, Kim GI, Davis A, et al. Activation of an IL6 inflammatory loop mediates trastuzumab resistance in HER2+ breast cancer by expanding the cancer stem cell population. Mol Cell 2012; 47(4): 570-84.
123. [123] Ginestier C, Liu S, Diebel ME, et al. CXCR1 blockade selectively targets human breast cancer stem cells in vitro and in xenografts. J Clin Investigation 2010; 120(2): 485-97.
124. [124] Gao H, Chakraborty G, Lee-Lim AP, et al. The BMP inhibitor Coco reactivates breast cancer cells at lung metastatic sites. Cell 2012; 150(4): 764-79.