Non-genetic cancer cell plasticity and therapy-induced stemness in tumour relapse: 'What does not kill me strengthens me'

British Journal of Cancer

Volumn 112, Issue 11, 2015, Pages 1725-1732

  Pisco, A O ^a,b   Huang, S ^a,b,c  

^a INSTITUTE FOR SYSTEMS BIOLOGY   (United States)

^b UNIVERSITY OF MANCHESTER   (United Kingdom)

^c UNIVERSITY OF CALGARY   (Canada)

Author keywords

cancer attractor; cell plasticity; epigenetic landscape; non genetic heterogeneity; therapy induced drug resistance

Indexed keywords

CANCER STEM CELL; CELL DIFFERENTIATION; CELL FATE; CELL KILLING; CELL POPULATION; CELL STRESS; CELL SURVIVAL; DEVELOPMENTAL GENE; EPIGENETICS; GENE EXPRESSION; GENE REGULATORY NETWORK; GENE SWITCHING; NERVE CELL PLASTICITY; PHENOTYPE; PRIORITY JOURNAL; REVIEW; STABLE EXPRESSION; THERAPY RESISTANCE; TUMOR RECURRENCE; ADJUVANT THERAPY; DRUG EFFECTS; DRUG RESISTANCE; GENETIC SELECTION; GENETICS; HUMAN; NEOPLASM RECURRENCE, LOCAL; NEOPLASMS; PATHOLOGY; SIGNAL TRANSDUCTION;

CELL SURVIVAL; DRUG RESISTANCE, NEOPLASM; HUMANS; NEOADJUVANT THERAPY; NEOPLASM RECURRENCE, LOCAL; NEOPLASMS; NEOPLASTIC STEM CELLS; PHENOTYPE; SELECTION, GENETIC; SIGNAL TRANSDUCTION;

EID: 84930043885     PISSN: 00070920     EISSN: 15321827     Source Type: Journal    
DOI: 10.1038/bjc.2015.146     Document Type: Review

References (98)

1. Abolhoda A, Wilson AE, Ross H, Danenberg PV, Burt M, Scotto KW. (1999). Rapid activation of MDR1 gene expression in human metastatic sarcoma after in vivo exposure to doxorubicin. Clin Cancer Res 5: 3352-3356
2. Abubaker K, Latifi A, Luwor R, Nazaretian S, Zhu H, Quinn MA, Thompson EW, Findlay JK, Ahmed N. (2013). Short-Term single treatment of chemotherapy results in the enrichment of ovarian cancer stem cell-like cells leading to an increased tumor burden. Mol Cancer 12: 24
3. Andarawewa KL, Erickson AC, Chou WS, Costes SV, Gascard P, Mott JD, Bissell MJ, Barcellos-Hoff MH. (2007). Ionizing radiation predisposes nonmalignant human mammary epithelial cells to undergo transforming growth factor induced epithelial to mesenchymal transition. Cancer Res 67: 8662-8670
4. Baker EK, Johnstone RW, Zalcberg JR, El-Osta A. (2005). Epigenetic changes to the MDR1 locus in response to chemotherapeutic drugs. Oncogene 24: 8061-8075
5. Balachandran VP, Cavnar MJ, Zeng S, Bamboat ZM, Ocuin LM, Obaid H, Sorenson EC, Popow R, Ariyan C, Rossi F, Besmer P, Guo T, Antonescu CR, Taguchi T, Yuan J, Wolchok JD, Allison JP, DeMatteo RP. (2011). Imatinib potentiates antitumor T cell responses in gastro intestinal stromal tumor through the inhibition of Ido. NatMed 17: 1094-1100
6. Bates SE, Mickley LA, Chen YN, Richert N, Rudick J, Biedler JL, Fojo AT. (1989). Expression of a drug resistance gene in human neuroblastoma cell lines: modulation by retinoic acid-induced differentiation. Mol Cell Biol 9: 4337-4344
7. Blanpain C, Mohrin M, Sotiropoulou PA, Passegueá E. (2011). DNA-damage response in tissue-specific and cancer stem cells. Stem Cell 8: 16-29
8. Bortul R, Tazzari PL, Cappellini A, Tabellini G, Billi AM, Bareggi R, Manzoli L, Cocco L, Martelli AM. (2003). Constitutively active Akt1 protects HL60 leukemia cells from TRAIL-induced apoptosis through a mechanism involving NF-kB activation and cFLIPL up-regulation. Leukemia 17: 379-389
9. Brock A, Chang H, Huang S. (2009). Non-genetic heterogeneity-A mutationindependent driving force for the somatic evolution of tumours. Nat Rev Genet 10: 336-342
10. Camphausen K, Purow B, Sproull M, Scott T, Ozawa T, Deen DF, Tofilon PJ. (2005). Influence of in vivo growth on human glioma cell line gene expression: convergent profiles under orthotopic conditions. Proc Natl Acad Sci USA 102: 8287-8292
11. Chaffer CL, Weinberg RA. (2011). A perspective on cancer cell metastasis. Science 331: 1559-1564
12. Challen GA, Little MH. (2006). A side order of stem cells: the SP phenotype. Stem Cells 24: 3-12
13. Chang HH, Oh PY, Ingber DE, Huang S. (2006). Multistable and multistep dynamics in neutrophil differentiation. BMC Cell Biol 7: 11
14. Chang Q, Jurisica I, Do T, Hedley DW. (2011). Hypoxia predicts aggressive growth and spontaneous metastasis formation from orthotopically grown primary xenografts of human pancreatic cancer. Cancer Res 71: 3110-3120
15. Chaudhary PM, Roninson IB. (1993). Induction of multidrug resistance in human cells by transient exposure to different chemotherapeutic drugs. J Natl Cancer Inst 85: 632-639
16. Chin KV, Tanaka S, Darlington G, Pastan I, Gottesman MM. (1990). Heat shock and arsenite increase expression of the multidrug resistance (MDR1) gene in human renal carcinoma cells. J Biol Chem 265: 221-226
17. Ciocca DR, Fuqua SAW, Lock-Lim S, Toft DO, Welch WJ, McGuire WL. (1992). Response of human breast cancer cells to heat shock and chemotherapeutic drugs. Cancer Res 52: 3648-3654
18. Corrêa S, Binato R, Rocher Du B, Castelo-Branco MTL, Pizzatti L, Abdelhay E. (2012). Wnt/b-catenin pathway regulates ABCB1 transcription in chronic myeloid leukemia. BMC Cancer 12: 303
19. Dallas NA, Xia L, Fan F, Gray MJ, Gaur P, van Buren G2, Samuel S, Kim MP, Lim SJ, Ellis LM. (2009). Chemoresistant colorectal cancer cells, the cancer stem cell phenotype, and increased sensitivity to insulin-like growth factor-I receptor inhibition. Cancer Res 69: 1951-1957
20. Dean M, Fojo T, Bates S. (2005). Tumour stem cells and drug resistance. Nat Rev Cancer 5: 275-284
21. DeNicola GM, Karreth FA, Humpton TJ, Gopinathan A, Wei C, Frese K, Mangal D, Yu KH, Yeo CJ, Calhoun ES, Scrimieri F, Winter JM, Hruban RH, Iacobuzio-Donahue C, Kern SE, Blair IA, Tuveson DA. (2011). Oncogene-induced Nrf2 transcription promotes ROS detoxification and tumorigenesis. Nature 475: 106-109
22. Dirks P. (2010). Cancer stem cells: Invitation to a second round. Nature 466: 40-41
23. Donaldson SS, Gordon LF, Hahn GM. (1978). Protective effect of hyperthermia against the cytotoxicity of actinomycin D on Chinese hamster cells. Cancer Treat Rep 62: 1489-1495
24. Donnenberg VS, Donnenberg AD. (2005). Multiple drug resistance in cancer revisited: the cancer stem cell hypothesis. J Clin Pharmacol 45: 872-877
25. Gerlinger M, Rowan AJ, Horswell S, Larkin J, Endesfelder D, Gronroos E, Martinez P, Matthews N, Stewart A, Tarpey P, Varela I, Phillimore B, Begum S, McDonald NQ, Butler A, Jones D, Raine K, Latimer C, Santos CR, Nohadani M, Eklund AC, Spencer-Dene B, Clark G, Pickering L, Stamp G, Gore M, Szallasi Z, Downward J, Futreal PA, Swanton C. (2012). Intratumor heterogeneity and branched evolution revealed by multiregion sequencing. N Engl J Med 366: 883-892
26. Ghisolfi L, Keates AC, Hu X, Lee D-K, Li CJ. (2012). Ionizing radiation induces stemness in cancer cells. PLoS One 7: e43628
27. Greáen H, Lotfi K, Zackrisson A-L, Peterson C. (2003). Spontaneous reversal of p-glycoprotein expression in multidrug resistant cell lines. Pharmacol Toxicol 93: 297-304
28. Gupta PB, Chaffer CL, Weinberg RA. (2009). Cancer stem cells: mirage or reality? Nat Med 15: 1010-1012
29. Gupta PB, Fillmore CM, Jiang G, Shapira SD, Tao K, Kuperwasser C, Lander ES. (2011). Stochastic state transitions give rise to phenotypic equilibrium in populations of cancer cells. Cell 146: 633-644
30. Gupta PB, Onder TT, Jiang G, Tao K, Kuperwasser C, Weinberg RA, Lander ES. (2009). Identification of selective inhibitors of cancer stem cells by high-Throughput screening. Cell 138: 645-659
31. Halliday J, Helmy K, Pattwell SS, Pitter KL, LaPlant Q, Ozawa T, Holland EC. (2014). In vivo radiation response of proneural glioma characterized by protective p53 transcriptional program and proneural-mesenchymal shift. Proc Natl Acad Sci USA 111: 5248-5253
32. Hanahan D, Weinberg RA. (2011). Hallmarks of cancer: the next generation. Cell 144: 646-674
33. He K, Xu T, Xu Y, Ring A, Kahn M, Goldkorn A. (2014). Cancer cells acquire a drug resistant, highly tumorigenic, cancer stem-like phenotype through modulation of the PI3K/Akt/b-catenin/CBP pathway. Int J Cancer 134: 43-54
34. Heams T, Huneman P, Lecointre G, Silberstein M. (2014). Handbook of Evolutionary Thinking in the Sciences. Springer: Berlin, Germany
35. Hoek KS, Goding CR. (2010). Cancer stem cells versus phenotype-switching in melanoma. Pigment Cell Melanoma Res 23: 746-759
36. Huang S. (2009). Non-genetic heterogeneity of cells in development: more than just noise. Development 136: 3853-3862
37. Huang S. (2011). The molecular and mathematical basis of Waddington's epigenetic landscape: a framework for post-Darwinian biology? BioEssays 34: 149-157
38. Huang S. (2013). Genetic and non-genetic instability in tumor progression: link between the fitness landscape and the epigenetic landscape of cancer cells. Cancer Metast Rev 32: 423-448
39. Huang S. (2014). The war on cancer: lessons from the war on terror. Front Oncol 4: 293
40. Huang S, Ernberg I, Kauffman S. (2009). Cancer attractors: a systems view of tumors from a gene network dynamics and developmental perspective. Semin Cell Dev Biol 20: 869-876
41. Huang S, Hölzel M, Knijnenburg T, Schlicker A, Roepman P, McDermott U, Garnett M, Grernrum W, Sun C, Prahallad A, Groenendijk FH, Mittempergher L, Nijkamp W, Neefjes J, Salazar R, Dijke Ten P, Uramoto H, Tanaka F, Beijersbergen RL, Wessels LFA, Bernards R. (2012). MED12 controls the response to multiple cancer drugs through regulation of TGFb receptor signaling. Cell 151: 937-950
42. Iliopoulos D, Hirsch HA, Wang G, Struhl K. (2011). Inducible formation of breast cancer stem cells and their dynamic equilibrium with non-stem cancer cells via IL6 secretion. Proc Natl Acad Sci USA 108: 1397-1402
43. Iyer R, Lehnert BE. (2002). Low dose, low-LET ionizing radiation-induced radioadaptation and associated early responses in unirradiated cells. Mutat Res 503: 1-9
44. Jackson TR, Salmina K, Huna A, Inashkina I, Jankevics E, Riekstina U, Kalnina Z, Ivanov A, Townsend PA, Cragg MS, Erenpreisa J. (2013). DNA damage causes TP53-dependent coupling of self-renewal and senescence pathways in embryonal carcinoma cells. Cell Cycle 12: 430-441
45. Kaern M, Elston TC, Blake WJ, Collins JJ. (2005). Stochasticity in gene expression: from theories to phenotypes. Nat Rev Genet 6: 451-464
46. Kauffman S. (1971). Differentiation of malignant to benign cells. J Theoret Biol 31: 429-451
47. Kenyon J, Gerson SL. (2007). The role of DNA damage repair in aging of adult stem cells. Nucleic Acids Res 35: 7557-7565
48. Kim M, Turnquist H, Jackson J, Sgagias M, Yan Y, Gong M, Dean M, Sharp JG, Cowan K. (2002). The multidrug resistance transporter ABCG2 (breast cancer resistance protein 1) effluxes Hoechst 33342 and is overexpressed in hematopoietic stem cells. Clin Cancer Res 8: 22-28
49. Kim Y, Kim KH, Lee J, Lee Y-A, Kim M, Lee SJ, Park K, Yang H, Jin J, Joo KM, Lee J, Nam D-H. (2012). Wnt activation is implicated in glioblastoma radioresistance. Lab Invest 92: 466-473
50. Lagadec C, Vlashi E, Donna Della L, Dekmezian C, Pajonk F. (2012). Radiationinduced reprogramming of breast cancer cells. Stem Cells 30: 833-844
51. Lee G-Y, Shim J-S, Cho B, Jung J-Y, Lee D-S, Oh I-H. (2010). Stochastic acquisition of a stem cell-like state and drug tolerance in leukemia cells stressed by radiation. Int J Hematol 93: 27-35
52. Li Q-Q, Xu J-D, Wang W-J, Cao X-X, Chen Q, Tang F, Chen Z-Q, Liu X-P, Xu Z-D. (2009). Twist1-mediated adriamycin-induced epithelial-mesenchymal transition relates to multidrug resistance and invasive potential in breast cancer cells. Clin Cancer Res 15: 2657-2665
53. Liao D, Esteávez-Salmeron L, Tlsty TD. (2012). Conceptualizing a tool to optimize therapy based on dynamic heterogeneity. Phys Biol 9: 065005
54. Liu J, Pan S, Hsieh MH, Ng N, Sun F, Wang T, Kasibhatla S, Schuller AG, Li AG, Cheng D, Li J, Tompkins C, Pferdekamper A, Steffy A, Cheng J, Kowal C, Phung V, Guo G, Wang Y, Graham MP, Flynn S, Brenner JC, Li C, Villarroel MC, Schultz PG, Wu X, McNamara P, Sellers WR, Petruzzelli L, Boral AL, Seidel HM, McLaughlin ME, Che J, Carey TE, Vanasse G, Harris JL. (2013). Targeting Wnt-driven cancer through the inhibition of Porcupine by LGK974. Proc Natl Acad Sci USA 110: 20224-20229
55. Mack SC, Witt H, Piro RM, Gu L, Zuyderduyn S, Stütz AM, Wang X, Gallo M, Garzia L, Zayne K, Zhang X, Ramaswamy V, Jäger N, Jones DTW, Sill M, Pugh TJ, Ryzhova M, Wani KM, Shih DJH, Head R, Remke M, Bailey SD, Zichner T, Faria CC, Barszczyk M, Stark S, Seker-Cin H, Hutter S, Johann P, Bender S, Hovestadt V, Tzaridis T, Dubuc AM, Northcott PA, Peacock J, Bertrand KC, Agnihotri S, Cavalli FMG, Clarke I, Nethery-Brokx K, Creasy CL, Verma SK, Koster J, Wu X, Yao Y, Milde T, Sin-Chan P, Zuccaro J, Lau L, Pereira S, Castelo-Branco P, Hirst M, Marra MA, Roberts SS, Fults D, Massimi L, Cho YJ, Van Meter T, Grajkowska W, Lach B, Kulozik AE, Deimling von A, Witt O, Scherer SW, Fan X, Muraszko KM, Kool M, Pomeroy SL, Gupta N, Phillips J, Huang A, Tabori U, Hawkins C, Malkin D, Kongkham PN, Weiss WA, Jabado N, Rutka JT, Bouffet E, Korbel JO, Lupien M, Aldape KD, Bader GD, Eils R, Lichter P, Dirks PB, Pfister SM, Korshunov A, Taylor MD. (2014). Epigenomic alterations define lethal CIMP-positive ependymomas of infancy. Nature 506: 445-450
56. Mayr E. (1972). Lamarck revisited. J Hist Biol 5: 55-94
57. McDunn JE. (2005). That which does not kill you makes you stronger: a molecular mechanism for preconditioning. Sci STKE 2005: pe34-pe34
58. Medema JP. (2013). Cancer stem cells: the challenges ahead. Nat Cell Biol 15: 338-344
59. Nakasone ES, Askautrud HA, Kees T, Park JH, Plaks V, Ewald AJ, Fein M, Rasch MG, Tan YX, Qiu J, Park J, Sinha P, Bissell MJ, Frengen E, Werb Z, Egeblad M. (2012). Imaging tumor-stroma interactions during chemotherapy reveals contributions of the microenvironment to resistance. Cancer Cell 21: 488-503
60. Notarbartolo M, Cervello M, Dusonchet L, Cusimano A, D'Alessandro N. (2002). Resistance to diverse apoptotic triggers in multidrug resistant HL60 cells and its possible relationship to the expression of P-glycoprotein, Fas and of the novel anti-Apoptosis factors IAP (inhibitory of apoptosis proteins). Cancer Lett 180: 91-101
61. Nowak MA. (2006). Evolutionary Dynamics. Harvard University Press: Cambridge, MA, USA
62. Nowell PC. (1976). The clonal evolution of tumor cell populations. Science 194: 23-28
63. Nör C, Zhang Z, Warner KA, Bernardi L, Visioli F, Helman JI, Roesler R, Nör JE. (2014). Cisplatin induces Bmi-1 and enhances the stem cell fraction in head and neck cancer. Neoplasia 16: 137-146
64. Pajic M, Iyer JK, Kersbergen A, van der Burg E, Nygren AOH, Jonkers J, Borst P, Rottenberg S. (2009). Moderate increase in Mdr1a/1b expression causes in vivo resistance to doxorubicin in a mouse model for hereditary breast cancer. Cancer Res 69: 6396-6404
65. Pardoll DM. (2012). The blockade of immune checkpoints in cancer immunotherapy. Nat Rev Cancer 12: 252-264
66. Pirozzi G, Tirino V, Camerlingo R, Franco R. (2011). Epithelial to mesenchymal transition by TGFb-1 induction increases stemness characteristics in primary non small cell lung cancer cell line. PLoS One 6: e21548
67. Pisco AO, Brock A, Zhou J, Moor A, Mojtahedi M, Jackson D, Huang S. (2013). Non-Darwinian dynamics in therapy-induced cancer drug resistance. Nat Commun 4: 2467
68. Pisco AO, Jackson DA, Huang S. (2014). Reduced intracellular drug accumulation in drug-resistant leukemia cells is not only solely due to MDR-mediated efflux but also to decreased uptake. Front Oncol 4: 306
69. Polyak K, Weinberg RA. (2009). Transitions between epithelial and mesenchymal states: acquisition of malignant and stem cell traits. Nat Rev Cancer 9: 265-273
70. Raj A, van Oudenaarden A. (2008). Nature, nurture, or chance: stochastic gene expression and its consequences. Cell 135: 216-226
71. Razandi M, Pedram A, Jordan VC, Fuqua S, Levin ER. (2012). Tamoxifen regulates cell fate through mitochondrial estrogen receptor beta in breast cancer. Oncogene 32: 3274-3285
72. Roesch A, Fukunaga-Kalabis M, Schmidt EC, Zabierowski SE, Brafford PA, Vultur A, Basu D, Gimotty P, Vogt T, Herlyn M. (2010). A temporarily distinct subpopulation of slow-cycling melanoma cells is required for continuous tumor growth. Cell 141: 583-594
73. Rosenzweig SA. (2012). Acquired resistance to drugs targeting receptor tyrosine kinases. Biochem Pharmacol 83: 1041-1048
74. Scharovsky OG, Mainetti LE, Rozados VR. (2009). Metronomic chemotherapy: changing the paradigm that more is better. Curr Oncol 16: 7-15
75. Sell S. (2004). Stem cell origin of cancer and differentiation therapy. Crit Rev Oncol Hematol 51(1): 1-28
76. Sharma SV, Lee DY, Li B, Quinlan MP, Takahashi F, Maheswaran S, McDermott U, Azizian N, Zou L, Fischbach MA, Wong K-K, Brandstetter K, Wittner B, Ramaswamy S, Classon M, Settleman J. (2010). A chromatin-mediated reversible drug-Tolerant state in cancer cell subpopulations. Cell 141: 69-80
77. Sherr CJ. (1996). Cancer cell cycles. Science 274: 1672-1677
78. Shlush LI, Zandi S, Mitchell A, Chen WC, Brandwein JM, Gupta V, Kennedy JA, Schimmer AD, Schuh AC, Yee KW, McLeod JL, Doedens M, Medeiros JJF, Marke R, Kim HJ, Lee K, McPherson JD, Hudson TJ. HALT Pan-Leukemia Gene Panel ConsortiumBrown AMK, Yousif F, Trinh QM, Stein LD, Minden MD, Wang JCY, Dick JE. (2014). Identification of pre-leukaemic haematopoietic stem cells in acute leukaemia. Nature 506: 328-333
79. Singh A, Settleman J. (2010). EMT, cancer stem cells and drug resistance: an emerging axis of evil in the war on cancer. Oncogene 29: 4741-4751
80. Sottoriva A, Kang H, Ma Z, Graham TA, Salomon MP, Zhao J, Marjoram P, Siegmund K, Press MF, Shibata D, Curtis C. (2015). A Big Bang model of human colorectal tumor growth. Nat Genet 47: 209-216
81. Sottoriva A, Spiteri I, Piccirillo SGM, Touloumis A, Collins VP, Marioni JC, Curtis C, Watts C, Tavareá S. (2013). Intratumor heterogeneity in human glioblastoma reflects cancer evolutionary dynamics. Proc Natl Acad Sci USA 110: 4009-4014
82. Stein U. (2001). Hyperthermia-induced nuclear translocation of transcription factor YB-1 leads to enhanced expression of multidrug resistance-related abc transporters. J Biol Chem 276: 28562-28569
83. Stein U, Fleuter C, Siegel F, Smith J, Kopacek A, Scudiero DA, Hite KM, Schlag PM, Shoemaker RH, Walther W. (2012). Impact of mutant b-catenin on ABCB1 expression and therapy response in colon cancer cells. Br J Cancer 106: 1395-1405
84. Sun C, Wang L, Huang S, Heynen GJJE, Prahallad A, Robert C, Haanen J, Blank C, Wesseling J, Willems SM, Zecchin D, Hobor S, Bajpe PK, Lieftink C, Mateus C, Vagner S, Grernrum W, Hofland I, Schlicker A, Wessels LFA, Beijersbergen RL, Bardelli A, Di Nicolantonio F, Eggermont AMM, Bernards R. (2014). Reversible and adaptive resistance to BRAF(V600E) inhibition in melanoma. Nature 508: 118-122
85. Taube JH, Herschkowitz JI, Komurov K, Zhou AY, Gupta S, Yang J, Hartwell K, Onder TT, Gupta PB, Evans KW, Hollier BG, Ram PT, Lander ES, Rosen JM, Weinberg RA, Mani SA. (2010). Core epithelial-Tomesenchymal transition interactome gene-expression signature is associated with claudin-low and metaplastic breast cancer subtypes. Proc Natl Acad Sci USA 107: 15449-15454
86. Tenbaum SP, Ordonez-Moran P, Puig I, Chicote I, Arques O, Landolfi S, Fernandez Y, Herance JR, Gispert JD, Mendizabal L, Aguilar S, Cajal SR, Schwartz SJ, Vivancos A, Espin E, Rojas S, Baselga J, Tabernero J, Munoz A, Palmer HG. (2012). Beta-catenin confers resistance to PI3K and AKT inhibitors and subverts FOXO3a to promote metastasis in colon cancer. Nat Med 18: 892-901
87. Das Thakur M, Salangsang F, Landman AS, Sellers WR, Pryer NK, Levesque MP, Dummer R, McMahon M, Stuart DD. (2013). Modelling vemurafenib resistance in melanoma reveals a strategy to forestall drug resistance. Nature 494: 251-255
88. Vogelstein B, Kinzler KW. (1993). The multistep nature of cancer. Trends Genet 9: 138-141
89. Waddington CH. (1942). Canalization of development and the inheritance of acquired characters. Nature 3811: 563-565
90. Waddington CH. (1956). Principles of Embryology. Allen & Unwind: London, UK
91. Wallner K, Li GC. (1986). Adriamycin resistance, heat resistance and radiation response in Chinese hamster fibroblasts. Int J Radiat Oncol Biol Phys 12: 829-833
92. Xia L, Zhang D, Du R, Pan Y, Zhao L, Sun S, Hong L, Liu J, Fan D. (2008). MiR-15b and miR-16 modulate multidrug resistance by targeting BCL2 in human gastric cancer cells. Int J Cancer 123: 372-379
93. Xue Z, Yan H, Li J, Liang S, Cai X, Chen X, Wu Q, Gao L, Wu K, Nie Y, Fan D. (2011). Identification of cancer stem cells in vincristine preconditioned SGC7901 gastric cancer cell line. J Cell Biochem 113: 302-312
94. Yachida S, Jones S, Bozic I, Antal T, Leary R, Fu B, Kamiyama M, Hruban RH, Eshleman JR, Nowak MA, Velculescu VE, Kinzler KW, Vogelstein B, Iacobuzio-Donahue CA. (2010). Distant metastasis occurs late during the genetic evolution of pancreatic cancer. Nature 467: 1114-1117
95. Yamada T, Takaoka AS, Naishiro Y, Hayashi R, Maruyama K, Maesawa C, Ochiai A, Hirohashi S. (2000). Transactivation of the multidrug resistance 1 gene by T-cell factor 4/beta-catenin complex in early colorectal carcinogenesis. Cancer Res 60: 4761-4766
96. Zhou JX, Aliyu MDS, Aurell E, Huang S. (2012). Quasi-potential landscape in complex multi-stable systems. J R Soc Interf 9: 3539-3553
97. Zhou JX, Pisco AO, Qian H, Huang S. (2014). Nonequilibrium population dynamics of phenotype conversion of cancer cells. PLoS ONE 9: e110714
98. Zhou S, Schuetz JD, Bunting KD, Colapietro AM, Sampath J, Morris JJ, Lagutina I, Grosveld GC, Osawa M, Nakauchi H, Sorrentino BP. (2001). The ABC transporter Bcrp1/ABCG2 is expressed in a wide variety of stem cells and is a molecular determinant of the side-population phenotype. Nat Med 7: 1028-1034