New findings on breast cancer stem cells: A review

Journal of Breast Cancer

Volumn 18, Issue 4, 2015, Pages 303-312

  Bozorgi, Azam ^a   Khazaei, Mozafar ^a   Khazaei, Mohammad Rasool ^a  

^a KERMANSHAH UNIVERSITY OF MEDICAL SCIENCES   (Iran)

Author keywords

Biological markers; Breast neoplasms; Neoplastic stem cells

Indexed keywords

ANGIOGENESIS; AUTOPHAGY; BREAST CANCER; CANCER RADIOTHERAPY; CARCINOGENICITY; DNA METHYLATION; DNA REPAIR; EPITHELIAL MESENCHYMAL TRANSITION; HUMAN; OXYGEN TENSION; PHENOTYPE; REVIEW; SIGNAL TRANSDUCTION; STEM CELL; TUMOR MICROENVIRONMENT;

EID: 84957660724     PISSN: 17386756     EISSN: 20929900     Source Type: Journal    
DOI: 10.4048/jbc.2015.18.4.303     Document Type: Review

References (132)

1. Torre LA, Bray F, Siegel RL, Ferlay J, Lortet-Tieulent J, Jemal A. Global cancer statistics, 2012. CA Cancer J Clin 2015;65:87-108.
2. Siegel R, Ma J, Zou Z, Jemal A. Cancer statistics, 2014. CA Cancer J Clin 2014;64:9-29.
3. Early Breast Cancer Trialists’ Collaborative Group (EBCTCG). Effects of chemotherapy and hormonal therapy for early breast cancer on recurrence and 15-year survival: an overview of the randomised trials. Lancet 2005;365:1687-717.
4. Clarke MF, Dick JE, Dirks PB, Eaves CJ, Jamieson CH, Jones DL, et al. Cancer stem cells: perspectives on current status and future directions: AACR Workshop on cancer stem cells. Cancer Res 2006;66:9339-44.
5. Hartwig FP, Nedel F, Collares T, Tarquinio SB, Nör JE, Demarco FF. Oncogenic somatic events in tissue-specific stem cells: a role in cancer recurrence? Ageing Res Rev 2014;13:100-6.
6. Wang RA, Li ZS, Zhang HZ, Zheng PJ, Li QL, Shi JG, et al. Invasive cancers are not necessarily from preformed in situ tumours: an alternative way of carcinogenesis from misplaced stem cells. J Cell Mol Med 2013;17:921-6.
7. Mintz B, Cronmiller C, Custer RP. Somatic cell origin of teratocarcinomas. Proc Natl Acad Sci U S A 1978;75:2834-8.
8. Gorden BH, Kim JH, Sarver AL, Frantz AM, Breen M, Lindblad-Toh K, et al. Identification of three molecular and functional subtypes in canine hemangiosarcoma through gene expression profiling and progenitor cell characterization. Am J Pathol 2014;184:985-95.
9. Al-Hajj M, Wicha MS, Benito-Hernandez A, Morrison SJ, Clarke MF. Prospective identification of tumorigenic breast cancer cells. Proc Natl Acad Sci U S A 2003;100:3983-8.
10. Ponti D, Costa A, Zaffaroni N, Pratesi G, Petrangolini G, Coradini D, et al. Isolation and in vitro propagation of tumorigenic breast cancer cells with stem/progenitor cell properties. Cancer Res 2005;65:5506-11.
11. Wright MH, Calcagno AM, Salcido CD, Carlson MD, Ambudkar SV, Varticovski L. BRCA1 breast tumors contain distinct CD44+/CD24- and CD133+ cells with cancer stem cell characteristics. Breast Cancer Res 2008;10:R10.
12. Perrone G, Gaeta LM, Zagami M, Nasorri F, Coppola R, Borzomati D, et al. In situ identification of CD44+/CD24- cancer cells in primary human breast carcinomas. PLoS One 2012;7:e43110.
13. Wang LB, He YQ, Wu LG, Chen DM, Fan H, Jia W. Isolation and characterization of human breast tumor stem cells. Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi 2012;28:1261-4.
14. Herrera-Gayol A, Jothy S. Adhesion proteins in the biology of breast cancer: contribution of CD44. Exp Mol Pathol 1999;66:149-56.
15. Rangaswami H, Bulbule A, Kundu GC. Osteopontin: role in cell signaling and cancer progression. Trends Cell Biol 2006;16:79-87.
16. Götte M, Yip GW. Heparanase, hyaluronan, and CD44 in cancers: a breast carcinoma perspective. Cancer Res 2006;66:10233-7.
17. Schabath H, Runz S, Joumaa S, Altevogt P. CD24 affects CXCR4 function in pre-B lymphocytes and breast carcinoma cells. J Cell Sci 2006;119(Pt 2):314-25.
18. Pattabiraman DR, Weinberg RA. Tackling the cancer stem cells: what challenges do they pose? Nat Rev Drug Discov 2014;13:497-512.
19. Ginestier C, Hur MH, Charafe-Jauffret E, Monville F, Dutcher J, Brown M, 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;1:555-67.
20. Balicki D. Moving forward in human mammary stem cell biology and breast cancer prognostication using ALDH1. Cell Stem Cell 2007;1: 485-7.
21. Chute JP, Muramoto GG, Whitesides J, Colvin M, Safi R, Chao NJ, et al. Inhibition of aldehyde dehydrogenase and retinoid signaling induces the expansion of human hematopoietic stem cells. Proc Natl Acad Sci U S A 2006;103:11707-12.
22. Meyer MJ, Fleming JM, Lin AF, Hussnain SA, Ginsburg E, Vonderhaar BK. CD44posCD49fhiCD133/2hi defines xenograft-initiating cells in estrogen receptor-negative breast cancer. Cancer Res 2010;70:4624-33.
23. Cariati M, Naderi A, Brown JP, Smalley MJ, Pinder SE, Caldas C, et al. Alpha-6 integrin is necessary for the tumourigenicity of a stem cell-like subpopulation within the MCF7 breast cancer cell line. Int J Cancer 2008;122:298-304.
24. Vaillant F, Asselin-Labat ML, Shackleton M, Forrest NC, Lindeman GJ, Visvader JE. The mammary progenitor marker CD61/beta3 integrin identifies cancer stem cells in mouse models of mammary tumorigenesis. Cancer Res 2008;68:7711-7.
25. Peitzsch C, Kurth I, Kunz-Schughart L, Baumann M, Dubrovska A. Discovery of the cancer stem cell related determinants of radioresistance. Radiother Oncol 2013;108:378-87.
26. Karamboulas C, Ailles L. Developmental signaling pathways in cancer stem cells of solid tumors. Biochim Biophys Acta 2013;1830:2481-95.
27. Muñoz P, Iliou MS, Esteller M. Epigenetic alterations involved in cancer stem cell reprogramming. Mol Oncol 2012;6:620-36.
28. Ling L, Nurcombe V, Cool SM. Wnt signaling controls the fate of mesenchymal stem cells. Gene 2009;433:1-7.
29. Liu S, Dontu G, Mantle ID, Patel S, Ahn NS, Jackson KW, et al. Hedgehog signaling and Bmi-1 regulate self-renewal of normal and malignant human mammary stem cells. Cancer Res 2006;66:6063-71.
30. Rizzo P, Osipo C, Foreman K, Golde T, Osborne B, Miele L. Rational targeting of Notch signaling in cancer. Oncogene 2008;27:5124-31.
31. Farnie G, Clarke RB. Mammary stem cells and breast cancer: role of Notch signalling. Stem Cell Rev 2007;3:169-75.
32. Yamanaka S. Induction of pluripotent stem cells from mouse fibroblasts by four transcription factors. Cell Prolif 2008;41 Suppl 1:51-6.
33. Rodriguez-Pinilla SM, Sarrio D, Moreno-Bueno G, Rodriguez-Gil Y, Martinez MA, Hernandez L, et al. Sox2: a possible driver of the basal-like phenotype in sporadic breast cancer. Mod Pathol 2007;20:474-81.
34. Leis O, Eguiara A, Lopez-Arribillaga E, Alberdi MJ, Hernandez-Garcia S, Elorriaga K, et al. Sox2 expression in breast tumours and activation in breast cancer stem cells. Oncogene 2012;31:1354-65.
35. Zhang J, Liang Q, Lei Y, Yao M, Li L, Gao X, et al. SOX4 induces epithelial-mesenchymal transition and contributes to breast cancer progression. Cancer Res 2012;72:4597-608.
36. Takahashi K, Tanabe K, Ohnuki M, Narita M, Ichisaka T, Tomoda K, et al. Induction of pluripotent stem cells from adult human fibroblasts by defined factors. Cell 2007;131:861-72.
37. Ben-Porath I, Thomson MW, Carey VJ, Ge R, Bell GW, Regev A, et al. An embryonic stem cell-like gene expression signature in poorly differentiated aggressive human tumors. Nat Genet 2008;40:499-507.
38. Stolzenburg S, Rots MG, Beltran AS, Rivenbark AG, Yuan X, Qian H, et al. Targeted silencing of the oncogenic transcription factor SOX2 in breast cancer. Nucleic Acids Res 2012;40:6725-40.
39. Lu X, Mazur SJ, Lin T, Appella E, Xu Y. The pluripotency factor nanog promotes breast cancer tumorigenesis and metastasis. Oncogene 2014;33:2655-64.
40. Luo W, Li S, Peng B, Ye Y, Deng X, Yao K. Embryonic stem cells markers SOX2, OCT4 and Nanog expression and their correlations with epithelial-mesenchymal transition in nasopharyngeal carcinoma. PLoS One 2013;8:e56324.
41. Singh A, Settleman J. EMT, cancer stem cells and drug resistance: an emerging axis of evil in the war on cancer. Oncogene 2010;29:4741-51.
42. Creighton CJ, Li X, Landis M, Dixon JM, Neumeister VM, Sjolund A, et al. Residual breast cancers after conventional therapy display mesenchymal as well as tumor-initiating features. Proc Natl Acad Sci USA 2009;106:13820-5.
43. Creighton CJ, Chang JC, Rosen JM. Epithelial-mesenchymal transition (EMT) in tumor-initiating cells and its clinical implications in breast cancer. J Mammary Gland Biol Neoplasia 2010;15:253-60.
44. Li QQ, Xu JD, Wang WJ, Cao XX, Chen Q, Tang F, et al. Twist1-mediated adriamycin-induced epithelial-mesenchymal transition relates to multidrug resistance and invasive potential in breast cancer cells. Clin Cancer Res 2009;15:2657-65.
45. Farmer P, Bonnefoi H, Anderle P, Cameron D, Wirapati P, Becette V, et al. A stroma-related gene signature predicts resistance to neoadjuvant chemotherapy in breast cancer. Nat Med 2009;15:68-74.
46. Thiery JP, Sleeman JP. Complex networks orchestrate epithelial-mesenchymal transitions. Nat Rev Mol Cell Biol 2006;7:131-42.
47. Hugo H, Ackland ML, Blick T, Lawrence MG, Clements JA, Williams ED, et al. Epithelial–mesenchymal and mesenchymal–epithelial transitions in carcinoma progression. J Cell Physiol 2007;213:374-83.
48. Hollier BG, Tinnirello AA, Werden SJ, Evans KW, Taube JH, Sarkar TR, et al. FOXC2 expression links epithelial-mesenchymal transition and stem cell properties in breast cancer. Cancer Res 2013;73:1981-92.
49. Cheng GZ, Chan J, Wang Q, Zhang W, Sun CD, Wang LH. Twist transcriptionally up-regulates AKT2 in breast cancer cells leading to increased migration, invasion, and resistance to paclitaxel. Cancer Res 2007;67:1979-87.
50. Hiscox S, Jiang WG, Obermeier K, Taylor K, Morgan L, Burmi R, et al. Tamoxifen resistance in MCF7 cells promotes EMT-like behaviour and involves modulation of beta-catenin phosphorylation. Int J Cancer 2006;118:290-301.
51. Borovski T, De Sousa E Melo F, Vermeulen L, Medema JP. Cancer stem cell niche: the place to be. Cancer Res 2011;71:634-9.
52. Korkaya H, Liu S, Wicha MS. Regulation of cancer stem cells by cytokine networks: attacking cancer’s inflammatory roots. Clin Cancer Res 2011;17:6125-9.
53. Brooks MD, Wicha MS. Tumor twitter: cellular communication in the breast cancer stem cell niche. Cancer Discov 2015;5:469-71.
54. Korkaya H, Kim GI, Davis A, Malik F, Henry NL, Ithimakin S, 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;47:570-84.
55. Bhola NE, Balko JM, Dugger TC, Kuba MG, Sánchez V, Sanders M, et al. TGF-beta inhibition enhances chemotherapy action against triple-negative breast cancer. J Clin Invest 2013;123:1348-58.
56. Ginestier C, Liu S, Diebel ME, Korkaya H, Luo M, Brown M, et al. CXCR1 blockade selectively targets human breast cancer stem cells in vitro and in xenografts. J Clin Invest 2010;120:485-97.
57. Azab AK, Runnels JM, Pitsillides C, Moreau AS, Azab F, Leleu X, et al. CXCR4 inhibitor AMD3100 disrupts the interaction of multiple myeloma cells with the bone marrow microenvironment and enhances their sensitivity to therapy. Blood 2009;113:4341-51.
58. Zeng Z, Samudio IJ, Munsell M, An J, Huang Z, Estey E, et al. Inhibition of CXCR4 with the novel RCP168 peptide overcomes stroma-mediated chemoresistance in chronic and acute leukemias. Mol Cancer Ther 2006;5:3113-21.
59. Dubrovska A, Elliott J, Salamone RJ, Telegeev GD, Stakhovsky AE, Schepotin IB, et al. CXCR4 expression in prostate cancer progenitor cells. PLoS One 2012;7:e31226.
60. Kuonen F, Secondini C, Rüegg C. Molecular pathways: emerging pathways mediating growth, invasion, and metastasis of tumors progressing in an irradiated microenvironment. Clin Cancer Res 2012; 18:5196-202.
61. Chung YL, Jian JJ, Cheng SH, Tsai SY, Chuang VP, Soong T, et al. Sublethal irradiation induces vascular endothelial growth factor and promotes growth of hepatoma cells: implications for radiotherapy of hepatocellular carcinoma. Clin Cancer Res 2006;12:2706-15.
62. Sofia Vala I, Martins LR, Imaizumi N, Nunes RJ, Rino J, Kuonen F, et al. Low doses of ionizing radiation promote tumor growth and metastasis by enhancing angiogenesis. PLoS One 2010;5:e11222.
63. Wardman P. Chemical radiosensitizers for use in radiotherapy. Clin Oncol (R Coll Radiol) 2007;19:397-417.
64. Batchelor TT, Gerstner ER, Emblem KE, Duda DG, Kalpathy-Cramer J, Snuderl M, et al. Improved tumor oxygenation and survival in glioblastoma patients who show increased blood perfusion after cediranib and chemoradiation. Proc Natl Acad Sci U S A 2013;110:19059-64.
65. Pece S, Tosoni D, Confalonieri S, Mazzarol G, Vecchi M, Ronzoni S, et al. Biological and molecular heterogeneity of breast cancers correlates with their cancer stem cell content. Cell 2010;140:62-73.
66. Cho KH, Choi MJ, Jeong KJ, Kim JJ, Hwang MH, Shin SC, et al. A ROS/STAT3/HIF-1alpha signaling cascade mediates EGF-induced TWIST1 expression and prostate cancer cell invasion. Prostate 2014;74:528-36.
67. Cojoc M, Peitzsch C, Trautmann F, Polishchuk L, Telegeev GD, Dubrovska A. Emerging targets in cancer management: role of the CXCL12/CXCR4 axis. Onco Targets Ther 2013;6:1347-61.
68. Qiang L, Wu T, Zhang HW, Lu N, Hu R, Wang YJ, et al. HIF-1alpha is critical for hypoxia-mediated maintenance of glioblastoma stem cells by activating Notch signaling pathway. Cell Death Differ 2012;19:284-94.
69. Choi H, Chun YS, Kim TY, Park JW. HIF-2alpha enhances beta-catenin/TCF-driven transcription by interacting with beta-catenin. Cancer Res 2010;70:10101-11.
70. Semenza GL. Hypoxia-inducible factors: mediators of cancer progression and targets for cancer therapy. Trends Pharmacol Sci 2012;33: 207-14.
71. Generali D, Berruti A, Brizzi MP, Campo L, Bonardi S, Wigfield S, et al. Hypoxia-inducible factor-1alpha expression predicts a poor response to primary chemoendocrine therapy and disease-free survival in primary human breast cancer. Clin Cancer Res 2006;12:4562-8.
72. DeGorter MK, Xia CQ, Yang JJ, Kim RB. Drug transporters in drug efficacy and toxicity. Annu Rev Pharmacol Toxicol 2012;52:249-73.
73. Gottesman MM, Fojo T, Bates SE. Multidrug resistance in cancer: role of ATP-dependent transporters. Nat Rev Cancer 2002;2:48-58.
74. Vasiliou V, Vasiliou K, Nebert DW. Human ATP-binding cassette (ABC) transporter family. Hum Genomics 2009;3:281-90.
75. Leonard GD, Fojo T, Bates SE. The role of ABC transporters in clinical practice. Oncologist 2003;8:411-24.
76. Huang WC, Hsieh YL, Hung CM, Chien PH, Chien YF, Chen LC, et al. BCRP/ABCG2 inhibition sensitizes hepatocellular carcinoma cells to sorafenib. PLoS One 2013;8:e83627.
77. Lecerf-Schmidt F, Peres B, Valdameri G, Gauthier C, Winter E, Payen L, et al. ABCG2: recent discovery of potent and highly selective inhibitors. Future Med Chem 2013;5:1037-45.
78. Stacy AE, Jansson PJ, Richardson DR. Molecular pharmacology of ABCG2 and its role in chemoresistance. Mol Pharmacol 2013;84:655-69.
79. Ma I, Allan AL. The role of human aldehyde dehydrogenase in normal and cancer stem cells. Stem Cell Rev 2011;7:292-306.
80. Young SZ, Bordey A. GABA’s control of stem and cancer cell proliferation in adult neural and peripheral niches. Physiology (Bethesda) 2009;24:171-85.
81. Singh S, Brocker C, Koppaka V, Chen Y, Jackson BC, Matsumoto A, et al. Aldehyde dehydrogenases in cellular responses to oxidative/electrophilic stress. Free Radic Biol Med 2013;56:89-101.
82. Croker AK, Goodale D, Chu J, Postenka C, Hedley BD, Hess DA, et al. High aldehyde dehydrogenase and expression of cancer stem cell markers selects for breast cancer cells with enhanced malignant and metastatic ability. J Cell Mol Med 2009;13:2236-52.
83. Magni M, Shammah S, Schiró R, Mellado W, Dalla-Favera R, Gianni AM. Induction of cyclophosphamide-resistance by aldehyde-dehydrogenase gene transfer. Blood 1996;87:1097-103.
84. Parajuli B, Fishel ML, Hurley TD. Selective ALDH3A1 inhibition by benzimidazole analogues increase mafosfamide sensitivity in cancer cells. J Med Chem 2014;57:449-61.
85. Tanei T, Morimoto K, Shimazu K, Kim SJ, Tanji Y, Taguchi T, 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. Clin Cancer Res 2009;15: 4234-41.
86. Cheung-Ong K, Giaever G, Nislow C. DNA-damaging agents in cancer chemotherapy: serendipity and chemical biology. Chem Biol 2013;20:648-59.
87. Al-Assar O, Mantoni T, Lunardi S, Kingham G, Helleday T, Brunner TB. Breast cancer stem-like cells show dominant homologous recombination due to a larger S-G2 fraction. Cancer Biol Ther 2011;11:1028-35.
88. Kim SY, Rhee JG, Song X, Prochownik EV, Spitz DR, Lee YJ. Breast cancer stem cell-like cells are more sensitive to ionizing radiation than non-stem cells: role of ATM. PLoS One 2012;7:e50423.
89. Brandsma I, Gent DC. Pathway choice in DNA double strand break repair: observations of a balancing act. Genome Integr 2012;3:9.
90. Jasin M, Rothstein R. Repair of strand breaks by homologous recombination. Cold Spring Harb Perspect Biol 2013;5:a012740.
91. Jackson SP. Sensing and repairing DNA double-strand breaks. Carcinogenesis 2002;23:687-96.
92. Niida H, Nakanishi M. DNA damage checkpoints in mammals. Mutagenesis 2006;21:3-9.
93. 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:e24080.
94. Sena LA, Chandel NS. Physiological roles of mitochondrial reactive oxygen species. Mol Cell 2012;48:158-67.
95. Cook JA, Gius D, Wink DA, Krishna MC, Russo A, Mitchell JB. Oxidative stress, redox, and the tumor microenvironment. Semin Radiat Oncol 2004;14:259-66.
96. Trachootham D, Alexandre J, Huang P. Targeting cancer cells by ROS-mediated mechanisms: a radical therapeutic approach? Nat Rev Drug Discov 2009;8:579-91.
97. Diehn M, Cho RW, Lobo NA, Kalisky T, Dorie MJ, Kulp AN, et al. Association of reactive oxygen species levels and radioresistance in cancer stem cells. Nature 2009;458:780-3.
98. Vanharanta S, Massagué J. Origins of metastatic traits. Cancer Cell 2013;24:410-21.
99. Del Mastro L, Clavarezza M, Venturini M. Reducing the risk of distant metastases in breast cancer patients: role of aromatase inhibitors. Cancer Treat Rev 2007;33:681-7.
100. Brown LF, Berse B, Van de Water L, Papadopoulos-Sergiou A, Perruzzi CA, Manseau EJ, et al. Expression and distribution of osteopontin in human tissues: widespread association with luminal epithelial surfaces. Mol Biol Cell 1992;3:1169-80.
101. Wai PY, Kuo PC. The role of osteopontin in tumor metastasis. J Surg Res 2004;121:228-41.
102. Chakraborty G, Jain S, Kundu GC. Osteopontin promotes vascular endothelial growth factor-dependent breast tumor growth and angiogenesis via autocrine and paracrine mechanisms. Cancer Res 2008;68:152-61.
103. 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;64:5702-11.
104. Tuck AB, Arsenault DM, O’Malley FP, Hota C, Ling MC, Wilson SM, et al. Osteopontin induces increased invasiveness and plasminogen activator expression of human mammary epithelial cells. Oncogene 1999;18:4237-46.
105. Kang Y, Siegel PM, Shu W, Drobnjak M, Kakonen SM, Cordón-Cardo C, et al. A multigenic program mediating breast cancer metastasis to bone. Cancer Cell 2003;3:537-49.
106. Oskarsson T, Acharyya S, Zhang XH, Vanharanta S, Tavazoie SF, Morris PG, et al. Breast cancer cells produce tenascin C as a metastatic niche component to colonize the lungs. Nat Med 2011;17:867-74.
107. Zhang XH, Wang Q, Gerald W, Hudis CA, Norton L, Smid M, et al. Latent bone metastasis in breast cancer tied to Src-dependent survival signals. Cancer Cell 2009;16:67-78.
108. Chen Q, Zhang XH, Massagué J. Macrophage binding to receptor VCAM-1 transmits survival signals in breast cancer cells that invade the lungs. Cancer Cell 2011;20:538-49.
109. Wu K, Fukuda K, Xing F, Zhang Y, Sharma S, Liu Y, et al. Roles of the cyclooxygenase 2 matrix metalloproteinase 1 pathway in brain metastasis of breast cancer. J Biol Chem 2015;290:9842-54.
110. Cojoc M, Mäbert K, Muders MH, Dubrovska A. A role for cancer stem cells in therapy resistance: cellular and molecular mechanisms. Semin Cancer Biol 2015;31:16-27.
111. Kroemer G, Mariño G, Levine B. Autophagy and the integrated stress response. Mol Cell 2010;40:280-93.
112. Parzych KR, Klionsky DJ. An overview of autophagy: morphology, mechanism, and regulation. Antioxid Redox Signal 2014;20:460-73.
113. McCarthy N. Autophagy: directed development. Nat Rev Cancer 2014;14:74-5.
114. Paglin S, Hollister T, Delohery T, Hackett N, McMahill M, Sphicas E, et al. A novel response of cancer cells to radiation involves autophagy and formation of acidic vesicles. Cancer Res 2001;61:439-44.
115. Yao KC, Komata T, Kondo Y, Kanzawa T, Kondo S, Germano IM. Molecular response of human glioblastoma multiforme cells to ionizing radiation: cell cycle arrest, modulation of the expression of cyclin-dependent kinase inhibitors, and autophagy. J Neurosurg 2003;98: 378-84.
116. Lu J, Sun D, Gao S, Gao Y, Ye J, Liu P. Cyclovirobuxine D induces autophagy-associated cell death via the Akt/mTOR pathway in MCF-7 human breast cancer cells. J Pharmacol Sci 2014;125:74-82.
117. Karantza-Wadsworth V, Patel S, Kravchuk O, Chen G, Mathew R, Jin S, et al. Autophagy mitigates metabolic stress and genome damage in mammary tumorigenesis. Genes Dev 2007;21:1621-35.
118. Mathew R, Kongara S, Beaudoin B, Karp CM, Bray K, Degenhardt K, et al. Autophagy suppresses tumor progression by limiting chromosomal instability. Genes Dev 2007;21:1367-81.
119. Ito H, Daido S, Kanzawa T, Kondo S, Kondo Y. Radiation-induced autophagy is associated with LC3 and its inhibition sensitizes malignant glioma cells. Int J Oncol 2005;26:1401-10.
120. Chaterjee M, van Golen KL. Breast cancer stem cells survive periods of farnesyl-transferase inhibitor-induced dormancy by undergoing autophagy. Bone Marrow Res 2011;2011:362938.
121. Rao R, Balusu R, Fiskus W, Mudunuru U, Venkannagari S, Chauhan L, et al. Combination of pan-histone deacetylase inhibitor and autophagy inhibitor exerts superior efficacy against triple-negative human breast cancer cells. Mol Cancer Ther 2012;11:973-83.
122. Gong C, Bauvy C, Tonelli G, Yue W, Deloménie C, Nicolas V, et al. Beclin 1 and autophagy are required for the tumorigenicity of breast cancer stem-like/progenitor cells. Oncogene 2013;32:2261-72.
123. Palacios F, Tushir JS, Fujita Y, D’Souza-Schorey C. Lysosomal targeting of E-cadherin: a unique mechanism for the down-regulation of cell-cell adhesion during epithelial to mesenchymal transitions. Mol Cell Biol 2005;25:389-402.
124. Sharif J, Muto M, Takebayashi S, Suetake I, Iwamatsu A, Endo TA, et al. The SRA protein Np95 mediates epigenetic inheritance by recruiting Dnmt1 to methylated DNA. Nature 2007;450:908-12.
125. van Vlerken LE, Hurt EM, Hollingsworth RE. The role of epigenetic regulation in stem cell and cancer biology. J Mol Med (Berl) 2012;90: 791-801.
126. Jin B, Ernst J, Tiedemann RL, Xu H, Sureshchandra S, Kellis M, et al. Linking DNA methyltransferases to epigenetic marks and nucleosome structure genome-wide in human tumor cells. Cell Rep 2012;2: 1411-24.
127. El Helou R, Wicinski J, Guille A, Adélaïde J, Finetti P, Bertucci F, et al. Brief reports: a distinct DNA methylation signature defines breast cancer stem cells and predicts cancer outcome. Stem Cells 2014;32: 3031-6.
128. Shukla S, Meeran SM. Epigenetics of cancer stem cells: pathways and therapeutics. Biochim Biophys Acta 2014;1840:3494-502.
129. Han M, Liu M, Wang Y, Chen X, Xu J, Sun Y, et al. Antagonism of miR-21 reverses epithelial-mesenchymal transition and cancer stem cell phenotype through AKT/ERK1/2 inactivation by targeting PTEN. PLoS One 2012;7:e39520.
130. Shimono Y, Zabala M, Cho RW, Lobo N, Dalerba P, Qian D, et al. Downregulation of miRNA-200c links breast cancer stem cells with normal stem cells. Cell 2009;138:592-603.
131. Gwak JM, Kim HJ, Kim EJ, Chung YR, Yun S, Seo AN, et al. MicroRNA-9 is associated with epithelial-mesenchymal transition, breast cancer stem cell phenotype, and tumor progression in breast cancer. Breast Cancer Res Treat 2014;147:39-49.
132. Taube JH, Malouf GG, Lu E, Sphyris N, Vijay V, Ramachandran PP, et al. Epigenetic silencing of microRNA-203 is required for EMT and cancer stem cell properties. Sci Rep 2013;3:2687.