REFERENCES
1. Pellegatti P, Raffaghello L, Bianchi G, Piccardi F, Pistoia V, Di Virgilio F. Increased level of extracellular ATP at tumor sites: in vivo imaging with plasma membrane luciferase. PLoS One 2008;3:e2599.
2. Wilhelm K, Ganesan J, Müller T, et al. Graft-versus-host disease is enhanced by extracellular ATP activating P2X7R. Nat Med 2010;16:1434-8.
3. Michaud M, Martins I, Sukkurwala AQ, et al. Autophagy-dependent anticancer immune responses induced by chemotherapeutic agents in mice. Science 2011;334:1573-7.
4. Falzoni S, Donvito G, Di Virgilio F. Detecting adenosine triphosphate in the pericellular space. Interface Focus 2013;3:20120101.
5. Morciano G, Sarti AC, Marchi S, et al. Use of luciferase probes to measure ATP in living cells and animals. Nat Protoc 2017;12:1542-62.
6. Liu Y, Zhang W, Cao Y, Liu Y, Bergmeier S, Chen X. Small compound inhibitors of basal glucose transport inhibit cell proliferation and induce apoptosis in cancer cells via glucose-deprivation-like mechanisms. Cancer Lett 2010;298:176-85.
7. Liu Y, Cao Y, Zhang W, et al. A small-molecule inhibitor of glucose transporter 1 downregulates glycolysis, induces cell-cycle arrest, and inhibits cancer cell growth in vitro and in vivo. Mol Cancer Ther 2012;11:1672-82.
8. Qian Y, Wang X, Liu Y, et al. Extracellular ATP is internalized by macropinocytosis and induces intracellular ATP increase and drug resistance in cancer cells. Cancer Lett 2014;351:242-51.
9. Qian Y, Wang X, Li Y, Cao Y, Chen X. Extracellular ATP a new player in cancer metabolism: NSCLC cells internalize ATP in vitro and in vivo using multiple endocytic mechanisms. Mol Cancer Res 2016;14:1087-96.
10. Wang X, Li Y, Qian Y, et al. Extracellular ATP, as an energy and phosphorylating molecule, induces different types of drug resistances in cancer cells through ATP internalization and intracellular ATP level increase. Oncotarget 2017;8:87860-77.
11. Wang X, Zhang H, Chen X. Drug resistance and combating drug resistance in cancer. Cancer Drug Resist 2019;2:141-60.
12. Cao Y, Wang X, Li Y, Evers M, Zhang H, Chen X. Extracellular and macropinocytosis internalized ATP work together to induce epithelial-mesenchymal transition and other early metastatic activities in lung cancer. Cancer Cell Int 2019;19:254.
13. Najafi M, Mortezaee K, Majidpoor J. Cancer stem cell (CSC) resistance drivers. Life Sci 2019;234:116781.
14. Begicevic RR, Falasca M. ABC transporters in cancer stem cells: beyond chemoresistance. Int J Mol Sci 2017;18:2362.
15. Cazet AS, Hui MN, Elsworth BL, et al. Targeting stromal remodeling and cancer stem cell plasticity overcomes chemoresistance in triple negative breast cancer. Nat Commun 2018;9:2897.
16. Mondal S, Bhattacharya K, Mandal C. Nutritional stress reprograms dedifferention in glioblastoma multiforme driven by PTEN/Wnt/Hedgehog axis: a stochastic model of cancer stem cells. Cell Death Discov 2018;4:110.
17. Filipponi D, Emelyanov A, Muller J, Molina C, Nichols J, Bulavin DV. DNA damage signaling-induced cancer cell reprogramming as a driver of tumor relapse. Mol Cell 2019;74:651-63.e8.
18. D'Alterio C, Scala S, Sozzi G, Roz L, Bertolini G. Paradoxical effects of chemotherapy on tumor relapse and metastasis promotion. Semin Cancer Biol 2020;60:351-61.
19. Lytle NK, Ferguson LP, Rajbhandari N, et al. A multiscale map of the stem cell state in pancreatic adenocarcinoma. Cell 2019;177:572-86.e22.
20. Visvader JE, Lindeman GJ. Cancer stem cells in solid tumours: accumulating evidence and unresolved questions. Nat Rev Cancer 2008;8:755-68.
21. Michor F, Polyak K. The origins and implications of intratumor heterogeneity. Cancer Prev Res (Phila) 2010;3:1361-4.
22. Meacham CE, Morrison SJ. Tumour heterogeneity and cancer cell plasticity. Nature 2013;501:328-37.
23. Ma S, Lee TK, Zheng BJ, Chan KW, Guan XY. CD133+ HCC cancer stem cells confer chemoresistance by preferential expression of the Akt/PKB survival pathway. Oncogene 2008;27:1749-58.
24. Mueller MT, Hermann PC, Witthauer J, et al. Combined targeted treatment to eliminate tumorigenic cancer stem cells in human pancreatic cancer. Gastroenterology 2009;137:1102-13.
26. Gupta PB, Fillmore CM, Jiang G, et al. Stochastic state transitions give rise to phenotypic equilibrium in populations of cancer cells. Cell 2011;146:633-44.
27. Dirkse A, Golebiewska A, Buder T, et al. Stem cell-associated heterogeneity in Glioblastoma results from intrinsic tumor plasticity shaped by the microenvironment. Nat Commun 2019;10:1787.
29. Dean M, Hamon Y, Chimini G. The human ATP-binding cassette (ABC) transporter superfamily. J Lipid Res 2001;42:1007-17.
30. Li YJ, Lei YH, Yao N, et al. Autophagy and multidrug resistance in cancer. Chin J Cancer 2017;36:52.
31. Kadioglu O, Saeed MEM, Munder M, Spuller A, Greten HJ, Efferth T. Effect of ABC transporter expression and mutational status on survival rates of cancer patients. Biomed Pharmacother 2020;131:110718.
32. Hu J, Li J, Yue X, et al. Expression of the cancer stem cell markers ABCG2 and OCT-4 in right-sided colon cancer predicts recurrence and poor outcomes. Oncotarget 2017;8:28463-70.
33. Robey RW, Pluchino KM, Hall MD, Fojo AT, Bates SE, Gottesman MM. Revisiting the role of ABC transporters in multidrug-resistant cancer. Nat Rev Cancer 2018;18:452-64.
34. 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;65:6207-19.
35. Ling X, Wu W, Fan C, et al. An ABCG2 non-substrate anticancer agent FL118 targets drug-resistant cancer stem-like cells and overcomes treatment resistance of human pancreatic cancer. J Exp Clin Cancer Res 2018;37:240.
36. Keshet GI, Goldstein I, Itzhaki O, et al. MDR1 expression identifies human melanoma stem cells. Biochem Biophys Res Commun 2008;368:930-6.
37. Gong F, Dong D, Zhang T, Xu W. Long non-coding RNA FENDRR attenuates the stemness of non-small cell lung cancer cells via decreasing multidrug resistance gene 1 (MDR1) expression through competitively binding with RNA binding protein HuR. Eur J Pharmacol 2019;853:345-52.
38. Xu H, Liu T, Li W, Yao Q. SMAR1 attenuates the stemness of osteosarcoma cells via through suppressing ABCG2 transcriptional activity. Environ Toxicol 2021;36:1090-8.
39. Stefan SM. Multi-target ABC transporter modulators: what next and where to go? Future Med Chem 2019;11:2353-8.
40. Chefetz I, Grimley E, Yang K, et al. A pan-ALDH1A inhibitor induces necroptosis in ovarian cancer stem-like cells. Cell Rep 2019;26:3061-75.e6.
41. Mazor G, Levin L, Picard D, et al. The lncRNA TP73-AS1 is linked to aggressiveness in glioblastoma and promotes temozolomide resistance in glioblastoma cancer stem cells. Cell Death Dis 2019;10:246.
42. 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.
43. Li Y, Chen T, Zhu J, Zhang H, Jiang H, Sun H. High ALDH activity defines ovarian cancer stem-like cells with enhanced invasiveness and EMT progress which are responsible for tumor invasion. Biochem Biophys Res Commun 2018;495:1081-8.
44. Singh S, Brocker C, Koppaka V, et al. Aldehyde dehydrogenases in cellular responses to oxidative/electrophilic stress. Free Radic Biol Med 2013;56:89-101.
45. Kim D, Choi BH, Ryoo IG, Kwak MK. High NRF2 level mediates cancer stem cell-like properties of aldehyde dehydrogenase (ALDH)-high ovarian cancer cells: inhibitory role of all-trans retinoic acid in ALDH/NRF2 signaling. Cell Death Dis 2018;9:896.
46. Harati M, Rodemann HP, Toulany M. Nanog signaling mediates radioresistance in ALDH-positive breast cancer cells. Int J Mol Sci 2019;20:1151.
47. Muralikrishnan V, Hurley TD, Nephew KP. Targeting aldehyde dehydrogenases to eliminate cancer stem cells in gynecologic malignancies. Cancers (Basel) 2020;12:961.
48. Chatterjee R, Chatterjee J. ROS and oncogenesis with special reference to EMT and stemness. Eur J Cell Biol 2020;99:151073.
49. Diehn M, Cho RW, Lobo NA, et al. Association of reactive oxygen species levels and radioresistance in cancer stem cells. Nature 2009;458:780-3.
50. Qian X, Nie X, Yao W, et al. Reactive oxygen species in cancer stem cells of head and neck squamous cancer. Semin Cancer Biol 2018;53:248-57.
51. Park HK, Hong JH, Oh YT, et al. Interplay between TRAP1 and Sirtuin-3 modulates mitochondrial respiration and oxidative stress to maintain stemness of glioma stem cells. Cancer Res 2019;79:1369-82.
52. Wu MJ, Chen YS, Kim MR, et al. Epithelial-mesenchymal transition directs stem cell polarity via regulation of mitofusin. Cell Metab 2019;29:993-1002.e6.
53. Huang H, Aladelokun O, Ideta T, Giardina C, Ellis LM, Rosenberg DW. Inhibition of PGE2/EP4 receptor signaling enhances oxaliplatin efficacy in resistant colon cancer cells through modulation of oxidative stress. Sci Rep 2019;9:4954.
54. Meng Q, Shi S, Liang C, et al. Abrogation of glutathione peroxidase-1 drives EMT and chemoresistance in pancreatic cancer by activating ROS-mediated Akt/GSK3β/Snail signaling. Oncogene 2018;37:5843-57.
55. Redza-Dutordoir M, Averill-Bates DA. Activation of apoptosis signalling pathways by reactive oxygen species. Biochim Biophys Acta 2016;1863:2977-92.
56. Townsend DM, Tew KD. The role of glutathione-S-transferase in anti-cancer drug resistance. Oncogene 2003;22:7369-75.
57. Lu H, Samanta D, Xiang L, et al. Chemotherapy triggers HIF-1-dependent glutathione synthesis and copper chelation that induces the breast cancer stem cell phenotype. Proc Natl Acad Sci U S A 2015;112:E4600-9.
58. Lan D, Wang L, He R, Ma J, Bin Y, Chi X, et al. Exogenous glutathione contributes to cisplatin resistance in lung cancer A549 cells. Am J Transl Res 2018;10:1295-309.
59. Akan I, Akan S, Akca H, Savas B, Ozben T. Multidrug resistance-associated protein 1 (MRP1) mediated vincristine resistance: effects of N-acetylcysteine and Buthionine sulfoximine. Cancer Cell Int 2005;5:22.
60. Bansal A, Simon MC. Glutathione metabolism in cancer progression and treatment resistance. J Cell Biol 2018;217:2291-8.
61. Boswell-Casteel RC, Fukuda Y, Schuetz JD. ABCB6, an ABC transporter impacting drug response and disease. AAPS J 2017;20:8.
62. Tong X, Zhao J, Zhang Y, Mu P, Wang X. Expression levels of MRP1, GST-π, and GSK3β in ovarian cancer and the relationship with drug resistance and prognosis of patients. Oncol Lett 2019;18:22-8.
63. Wang B, Shen C, Li Y, et al. Oridonin overcomes the gemcitabine resistant PANC-1/Gem cells by regulating GST pi and LRP/1 ERK/JNK signalling. Onco Targets Ther 2019;12:5751-65.
64. El-Readi MZ, Eid S, Abdelghany AA, Al-Amoudi HS, Efferth T, Wink M. Resveratrol mediated cancer cell apoptosis, and modulation of multidrug resistance proteins and metabolic enzymes. Phytomedicine 2019;55:269-81.
65. Chatterjee A, Gupta S. The multifaceted role of glutathione S-transferases in cancer. Cancer Lett 2018;433:33-42.
66. Yoshida GJ. Metabolic reprogramming: the emerging concept and associated therapeutic strategies. J Exp Clin Cancer Res 2015;34:111.
67. El-Sahli S, Wang L. Cancer stem cell-associated pathways in the metabolic reprogramming of breast cancer. Int J Mol Sci 2020;21:9125.
68. Fonseca NA, Cruz AF, Moura V, Simões S, Moreira JN. The cancer stem cell phenotype as a determinant factor of the heterotypic nature of breast tumors. Crit Rev Oncol Hematol 2017;113:111-21.
69. Luo M, Shang L, Brooks MD, et al. Targeting breast cancer stem cell state equilibrium through modulation of redox signaling. Cell Metab 2018;28:69-86.e6.
70. Shibue T, Weinberg RA. EMT, CSCs, and drug resistance: the mechanistic link and clinical implications. Nat Rev Clin Oncol 2017;14:611-29.
71. Dhawan A, Madani Tonekaboni SA, Taube JH, et al. Mathematical modelling of phenotypic plasticity and conversion to a stem-cell state under hypoxia. Sci Rep 2016;6:18074.
72. Emami Nejad A, Najafgholian S, Rostami A, et al. The role of hypoxia in the tumor microenvironment and development of cancer stem cell: a novel approach to developing treatment. Cancer Cell Int 2021;21:62.
73. Francesco EM, Sotgia F, Lisanti MP. Cancer stem cells (CSCs): metabolic strategies for their identification and eradication. Biochem J 2018;475:1611-34.
74. Zhao H, Duan Q, Zhang Z, et al. Up-regulation of glycolysis promotes the stemness and EMT phenotypes in gemcitabine-resistant pancreatic cancer cells. J Cell Mol Med 2017;21:2055-67.
75. Semenza GL. Hypoxia-inducible factors: coupling glucose metabolism and redox regulation with induction of the breast cancer stem cell phenotype. EMBO J 2017;36:252-9.
76. Qiang L, Wu T, Zhang HW, et al. HIF-1α is critical for hypoxia-mediated maintenance of glioblastoma stem cells by activating Notch signaling pathway. Cell Death Differ 2012;19:284-94.
77. Yeo CD, Kang N, Choi SY, et al. The role of hypoxia on the acquisition of epithelial-mesenchymal transition and cancer stemness: a possible link to epigenetic regulation. Korean J Intern Med 2017;32:589-99.
78. Zhang Z, Fang E, Rong Y, Han H, Gong Q, Xiao Y, et al. Hypoxia-induced lncRNA CASC9 enhances glycolysis and the epithelial-mesenchymal transition of pancreatic cancer by a positive feedback loop with AKT/HIF-1α signaling. Am J Cancer Res 2021;11:123-37.
79. Schöning JP, Monteiro M, Gu W. Drug resistance and cancer stem cells: the shared but distinct roles of hypoxia-inducible factors HIF1α and Hif-2α. Clin Exp Pharmacol Physiol 2017;44:153-61.
80. Nilsson MB, Sun H, Robichaux J, et al. A YAP/FOXM1 axis mediates EMT-associated EGFR inhibitor resistance and increased expression of spindle assembly checkpoint components. Sci Transl Med 2020;12:eaaz4589.
81. Demaria M, Giorgi C, Lebiedzinska M, Esposito G, D’Angeli L, Bartoli A, et al. A STAT3-mediated metabolic switch is involved in tumour transformation and STAT3 addiction. Aging 2010;2:823-42.
82. Folmes CD, Martinez-Fernandez A, Faustino RS, et al. Nuclear reprogramming with c-Myc potentiates glycolytic capacity of derived induced pluripotent stem cells. J Cardiovasc Transl Res 2013;6:10-21.
83. Das PK, Pillai S, Rakib MA, et al. Plasticity of cancer stem cell: origin and role in disease progression and therapy resistance. Stem Cell Rev Rep 2020;16:397-412.
84. Hirpara J, Eu JQ, Tan JKM, et al. Metabolic reprogramming of oncogene-addicted cancer cells to OXPHOS as a mechanism of drug resistance. Redox Biol 2019;25:101076.
85. Dar S, Chhina J, Mert I, et al. Bioenergetic adaptations in chemoresistant ovarian cancer cells. Sci Rep 2017;7:8760.
86. Onnis B, Rapisarda A, Melillo G. Development of HIF-1 inhibitors for cancer therapy. J Cell Mol Med 2009;13:2780-6.
87. Zhou Y, Zhou Y, Shingu T, et al. Metabolic alterations in highly tumorigenic glioblastoma cells: preference for hypoxia and high dependency on glycolysis. J Biol Chem 2011;286:32843-53.
88. Schornack PA, Gillies RJ. Contributions of cell metabolism and H+ diffusion to the acidic pH of tumors. Neoplasia 2003;5:135-45.
89. Corbet C, Feron O. Tumour acidosis: from the passenger to the driver's seat. Nat Rev Cancer 2017;17:577-93.
90. Riemann A, Rauschner M, Gießelmann M, Reime S, Haupt V, Thews O. Extracellular acidosis modulates the expression of Epithelial-Mesenchymal Transition (EMT) markers and adhesion of epithelial and tumor cells. Neoplasia 2019;21:450-8.
91. Linden C, Corbet C. Therapeutic targeting of cancer stem cells: integrating and exploiting the acidic niche. Front Oncol 2019;9:159.
92. Andreucci E, Peppicelli S, Ruzzolini J, et al. The acidic tumor microenvironment drives a stem-like phenotype in melanoma cells. J Mol Med (Berl) 2020;98:1431-46.
93. Ruzzolini J, Peppicelli S, Andreucci E, et al. Everolimus selectively targets vemurafenib resistant BRAFV600E melanoma cells adapted to low pH. Cancer Lett 2017;408:43-54.
94. Li Z, Bao S, Wu Q, et al. Hypoxia-inducible factors regulate tumorigenic capacity of glioma stem cells. Cancer Cell 2009;15:501-13.
95. Khacho M, Tarabay M, Patten D, et al. Acidosis overrides oxygen deprivation to maintain mitochondrial function and cell survival. Nat Commun 2014;5:3550.
96. Corbet C, Bastien E, Santiago de Jesus JP, et al. TGF-β2-induced formation of lipid droplets supports acidosis-driven EMT and the metastatic spreading of cancer cells. Nat Commun 2020;11:454.
97. Li J, Condello S, Thomes-Pepin J, et al. Lipid Desaturation is a metabolic marker and therapeutic target of ovarian cancer stem cells. Cell Stem Cell 2017;20:303-314.e5.
98. Thews O, Nowak M, Sauvant C, Gekle M. Hypoxia-induced extracellular acidosis increases p-glycoprotein activity and chemoresistance in tumors in vivo via p38 signaling pathway. Adv Exp Med Biol 2011;701:115-22.
99. Cheng GM, To KK. Adverse cell culture conditions mimicking the tumor microenvironment upregulate ABCG2 to mediate multidrug resistance and a more malignant phenotype. ISRN Oncol 2012;2012:746025.
100. Smith AG, Macleod KF. Autophagy, cancer stem cells and drug resistance. J Pathol 2019;247:708-18.
101. Kanamala M, Wilson WR, Yang M, Palmer BD, Wu Z. Mechanisms and biomaterials in pH-responsive tumour targeted drug delivery: A review. Biomaterials 2016;85:152-67.
102. Corbet C, Ragelle H, Pourcelle V, et al. Delivery of siRNA targeting tumor metabolism using non-covalent PEGylated chitosan nanoparticles: Identification of an optimal combination of ligand structure, linker and grafting method. J Control Release 2016;223:53-63.
103. Fitzwalter BE, Towers CG, Sullivan KD, et al. Autophagy inhibition mediates apoptosis sensitization in cancer therapy by relieving FOXO3a turnover. Dev Cell 2018;44:555-65.e3.
104. Liang C, Dong Z, Cai X, et al. Hypoxia induces sorafenib resistance mediated by autophagy via activating FOXO3a in hepatocellular carcinoma. Cell Death Dis 2020;11:1017.
105. Ho CJ, Gorski SM. Molecular mechanisms underlying autophagy-mediated treatment resistance in cancer. Cancers (Basel) 2019;11:1775.
106. Ryoo IG, Choi BH, Ku SK, Kwak MK. High CD44 expression mediates p62-associated NFE2L2/NRF2 activation in breast cancer stem cell-like cells: Implications for cancer stem cell resistance. Redox Biol 2018;17:246-58.
107. Jang JE, Eom JI, Jeung HK, et al. PERK/NRF2 and autophagy form a resistance mechanism against G9a inhibition in leukemia stem cells. J Exp Clin Cancer Res 2020;39:66.
108. Yao N, Wang C, Hu N, et al. Inhibition of PINK1/Parkin-dependent mitophagy sensitizes multidrug-resistant cancer cells to B5G1, a new betulinic acid analog. Cell Death Dis 2019;10:232.
109. Yan C, Li T-S. Dual role of mitophagy in cancer drug resistance. Anticancer Res 2018;38:617-21.
110. Liu K, Lee J, Kim JY, et al. Mitophagy controls the activities of tumor suppressor p53 to regulate hepatic cancer stem cells. Mol Cell 2017;68:281-92.e5.
111. Yan C, Luo L, Guo CY, et al. Doxorubicin-induced mitophagy contributes to drug resistance in cancer stem cells from HCT8 human colorectal cancer cells. Cancer Lett 2017;388:34-42.
112. Tam SY, Wu VWC, Law HKW. Hypoxia-induced epithelial-mesenchymal transition in cancers: HIF-1α and beyond. Front Oncol 2020;10:486.
113. Gjorevski N, Boghaert E, Nelson CM. Regulation of epithelial-mesenchymal transition by transmission of mechanical stress through epithelial tissues. Cancer Microenviron 2012;5:29-38.
114. Suarez-Carmona M, Lesage J, Cataldo D, Gilles C. EMT and inflammation: inseparable actors of cancer progression. Mol Oncol 2017;11:805-23.
115. Du B, Shim JS. Targeting epithelial-mesenchymal transition (EMT) to overcome drug resistance in cancer. Molecules 2016;21:965.
116. Jolly MK, Somarelli JA, Sheth M, et al. Hybrid epithelial/mesenchymal phenotypes promote metastasis and therapy resistance across carcinomas. Pharmacol Ther 2019;194:161-84.
117. Bocci F, Gearhart-Serna L, Boareto M, et al. Toward understanding cancer stem cell heterogeneity in the tumor microenvironment. Proc Natl Acad Sci U S A 2019;116:148-57.
118. Wilson MM, Weinberg RA, Lees JA, Guen VJ. Emerging mechanisms by which EMT programs control stemness. Trends Cancer 2020;6:775-80.
119. Wang Z, Sun H, Provaznik J, Hackert T, Zöller M. Pancreatic cancer-initiating cell exosome message transfer into noncancer-initiating cells: the importance of CD44v6 in reprogramming. J Exp Clin Cancer Res 2019;38:132.
120. Schuster N, Krieglstein K. Mechanisms of TGF-beta-mediated apoptosis. Cell Tissue Res 2002;307:1-14.
121. 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.
122. Tripathi V, Shin JH, Stuelten CH, Zhang YE. TGF-β-induced alternative splicing of TAK1 promotes EMT and drug resistance. Oncogene 2019;38:3185-200.
123. Xu X, Zhang L, He X, et al. TGF-β plays a vital role in triple-negative breast cancer (TNBC) drug-resistance through regulating stemness, EMT and apoptosis. Biochem Biophys Res Commun 2018;502:160-5.
124. Chaffer CL, Marjanovic ND, Lee T, et al. Poised chromatin at the ZEB1 promoter enables breast cancer cell plasticity and enhances tumorigenicity. Cell 2013;154:61-74.
125. Oshimori N, Oristian D, Fuchs E. TGF-β promotes heterogeneity and drug resistance in squamous cell carcinoma. Cell 2015;160:963-76.
126. Zhu X, Chen L, Liu L, Niu X. EMT-Mediated Acquired EGFR-TKI Resistance in NSCLC: Mechanisms and Strategies. Front Oncol 2019;9:1044.
127. Saxena M, Stephens MA, Pathak H, Rangarajan A. Transcription factors that mediate epithelial-mesenchymal transition lead to multidrug resistance by upregulating ABC transporters. Cell Death Dis 2011;2:e179.
128. Dong J, Zhai B, Sun W, Hu F, Cheng H, Xu J. Activation of phosphatidylinositol 3-kinase/AKT/snail signaling pathway contributes to epithelial-mesenchymal transition-induced multi-drug resistance to sorafenib in hepatocellular carcinoma cells. PLoS One 2017;12:e0185088.
129. Xu W, Yang Z, Lu N. A new role for the PI3K/Akt signaling pathway in the epithelial-mesenchymal transition. Cell Adh Migr 2015;9:317-24.
130. Karaosmanoğlu O, Banerjee S, Sivas H. Identification of biomarkers associated with partial epithelial to mesenchymal transition in the secretome of slug over-expressing hepatocellular carcinoma cells. Cell Oncol (Dordr) 2018;41:439-53.
131. Roh YG, Mun MH, Jeong MS, et al. Drug resistance of bladder cancer cells through activation of ABCG2 by FOXM1. BMB Rep 2018;51:98-103.
132. Yochum ZA, Cades J, Wang H, et al. Targeting the EMT transcription factor TWIST1 overcomes resistance to EGFR inhibitors in EGFR-mutant non-small-cell lung cancer. Oncogene 2019;38:656-70.
133. Paranjape AN, Soundararajan R, Werden SJ, et al. Inhibition of FOXC2 restores epithelial phenotype and drug sensitivity in prostate cancer cells with stem-cell properties. Oncogene 2016;35:5963-76.
134. Sun S, Yang X, Qin X, Zhao Y. TCF4 promotes colorectal cancer drug resistance and stemness via regulating ZEB1/ZEB2 expression. Protoplasma 2020;257:921-30.
135. Zhang P, Sun Y, Ma L. ZEB1: at the crossroads of epithelial-mesenchymal transition, metastasis and therapy resistance. Cell Cycle 2015;14:481-7.
136. Zhang X, Zhang Z, Zhang Q, et al. ZEB1 confers chemotherapeutic resistance to breast cancer by activating ATM. Cell Death Dis 2018;9:57.
137. Zhang P, Wei Y, Wang L, et al. ATM-mediated stabilization of ZEB1 promotes DNA damage response and radioresistance through CHK1. Nat Cell Biol 2014;16:864-75.
138. Espinoza I, Miele L. Deadly crosstalk: Notch signaling at the intersection of EMT and cancer stem cells. Cancer Lett 2013;341:41-5.
139. Poh ME, Liam CK, Rajadurai P, Chai CS. Epithelial-to-mesenchymal transition (EMT) causing acquired resistance to afatinib in a patient with epidermal growth factor receptor (EGFR)-mutant lung adenocarcinoma. J Thorac Dis 2018;10:E560-3.
140. Namba K, Shien K, Takahashi Y, et al. Activation of AXL as a preclinical acquired resistance mechanism against osimertinib treatment in EGFR-mutant non-small cell lung cancer cells. Mol Cancer Res 2019;17:499-507.
141. Zhou J, Wang J, Zeng Y, Zhang X, Hu Q, Zheng J, et al. Implication of epithelial-mesenchymal transition in IGF1R-induced resistance to EGFR-TKIs in advanced non-small cell lung cancer. Oncotarget 2015;6:44332-45.
142. Sato H, Yamamoto H, Sakaguchi M, et al. Combined inhibition of MEK and PI3K pathways overcomes acquired resistance to EGFR-TKIs in non-small cell lung cancer. Cancer Sci 2018;109:3183-96.
143. Otsuki Y, Saya H, Arima Y. Prospects for new lung cancer treatments that target EMT signaling. Dev Dyn 2018;247:462-72.
144. Cho ES, Kang HE, Kim NH, Yook JI. Therapeutic implications of cancer epithelial-mesenchymal transition (EMT). Arch Pharm Res 2019;42:14-24.
145. Wu X, Wu Q, Zhou X, Huang J. SphK1 functions downstream of IGF-1 to modulate IGF-1-induced EMT, migration and paclitaxel resistance of A549 cells: A preliminary in vitro study. J Cancer 2019;10:4264-9.
146. May CD, Sphyris N, Evans KW, Werden SJ, Guo W, Mani SA. Epithelial-mesenchymal transition and cancer stem cells: a dangerously dynamic duo in breast cancer progression. Breast Cancer Res 2011;13:202.
147. Jabbarzadeh Kaboli P, Salimian F, Aghapour S, et al. Akt-targeted therapy as a promising strategy to overcome drug resistance in breast cancer - a comprehensive review from chemotherapy to immunotherapy. Pharmacol Res 2020;156:104806.
148. Zhang Z, Han H, Rong Y, et al. Hypoxia potentiates gemcitabine-induced stemness in pancreatic cancer cells through AKT/Notch1 signaling. J Exp Clin Cancer Res 2018;37:291.
149. Mohapatra P, Shriwas O, Mohanty S, et al. CMTM6 drives cisplatin resistance by regulating Wnt signaling through the ENO-1/AKT/GSK3β axis. JCI Insight 2021;6:143643.
150. Yuan Z, Liang X, Zhan Y, et al. Targeting CD133 reverses drug-resistance via the AKT/NF-κB/MDR1 pathway in colorectal cancer. Br J Cancer 2020;122:1342-53.
151. Takebe N, Harris PJ, Warren RQ, Ivy SP. Targeting cancer stem cells by inhibiting Wnt, Notch, and Hedgehog pathways. Nat Rev Clin Oncol 2011;8:97-106.
152. Gu JW, Rizzo P, Pannuti A, Golde T, Osborne B, Miele L. Notch signals in the endothelium and cancer "stem-like" cells: opportunities for cancer therapy. Vasc Cell 2012;4:7.
153. Xiao W, Gao Z, Duan Y, Yuan W, Ke Y. Notch signaling plays a crucial role in cancer stem-like cells maintaining stemness and mediating chemotaxis in renal cell carcinoma. J Exp Clin Cancer Res 2017;36:41.
154. Lee CW, Raskett CM, Prudovsky I, Altieri DC. Molecular dependence of estrogen receptor-negative breast cancer on a notch-survivin signaling axis. Cancer Res 2008;68:5273-81.
155. Huang J, Chen Y, Li J, et al. Notch-1 Confers Chemoresistance in lung adenocarcinoma to taxanes through AP-1/microRNA-451 mediated regulation of MDR-1. Mol Ther Nucleic Acids 2016;5:e375.
156. Sun L, Ke J, He Z, et al. HES1 Promotes colorectal cancer cell resistance to 5-Fu by inducing of EMT and ABC transporter proteins. J Cancer 2017;8:2802-8.
157. Hu S, Fu W, Li T, et al. Antagonism of EGFR and Notch limits resistance to EGFR inhibitors and radiation by decreasing tumor-initiating cell frequency. Sci Transl Med 2017;9:eaag0339.
158. Baker A, Wyatt D, Bocchetta M, et al. Notch-1-PTEN-ERK1/2 signaling axis promotes HER2+ breast cancer cell proliferation and stem cell survival. Oncogene 2018;37:4489-504.
159. Yang Z, Guo L, Liu D, Sun L, Chen H, Deng Q, et al. Acquisition of resistance to trastuzumab in gastric cancer cells is associated with activation of IL-6/STAT3/Jagged-1/Notch positive feedback loop. Oncotarget 2014;6:5072-87.
160. Usui T, Sakurai M, Umata K, et al. Hedgehog signals mediate anti-cancer drug resistance in three-dimensional primary colorectal cancer organoid culture. Int J Mol Sci 2018;19:1098.
161. Cho Y, Kim YK. Cancer stem cells as a potential target to overcome multidrug resistance. Front Oncol 2020;10:764.
162. Zhang H, Hu L, Cheng M, Wang Q, Hu X, Chen Q. The Hedgehog signaling pathway promotes chemotherapy resistance via multidrug resistance protein 1 in ovarian cancer. Oncol Rep 2020;44:2610-20.
163. Zhou XT, Ding J, Li HY, et al. Hedgehog signalling mediates drug resistance through targeting TAP1 in hepatocellular carcinoma. J Cell Mol Med 2020;24:4298-311.
164. Po A, Citarella A, Catanzaro G, et al. Hedgehog-GLI signalling promotes chemoresistance through the regulation of ABC transporters in colorectal cancer cells. Sci Rep 2020;10:13988.
165. Periplocin from Cortex periplocae inhibits cell growth and down-regulates survivin and c-myc expression in colon cancer in vitro and in vivo via β-catenin/TCF signaling. Oncol Rep 2010:24.
166. Vesel M, Rapp J, Feller D, et al. ABCB1 and ABCG2 drug transporters are differentially expressed in non-small cell lung cancers (NSCLC) and expression is modified by cisplatin treatment via altered Wnt signaling. Respir Res 2017;18:52.
167. He L, Zhu H, Zhou S, et al. Wnt pathway is involved in 5-FU drug resistance of colorectal cancer cells. Exp Mol Med 2018;50:1-12.
168. Fukumoto T, Zhu H, Nacarelli T, et al. N6-Methylation of adenosine of FZD10 mRNA contributes to PARP inhibitor resistance. Cancer Res 2019;79:2812-20.
169. Yamamoto TM, McMellen A, Watson ZL, et al. Activation of Wnt signaling promotes olaparib resistant ovarian cancer. Mol Carcinog 2019;58:1770-82.
171. Chen G, Gao C, Gao X, et al. Wnt/β-catenin pathway activation mediates adaptive resistance to BRAF inhibition in colorectal cancer. Mol Cancer Ther 2018;17:806-13.
172. Solberg NT, Waaler J, Lund K, Mygland L, Olsen PA, Krauss S. TANKYRASE inhibition enhances the antiproliferative effect of PI3K and EGFR inhibition, mutually affecting β-CATENIN and AKT signaling in colorectal cancer. Mol Cancer Res 2018;16:543-53.
173. Park YL, Kim HP, Cho YW, et al. Activation of WNT/β-catenin signaling results in resistance to a dual PI3K/mTOR inhibitor in colorectal cancer cells harboring PIK3CA mutations. Int J Cancer 2019;144:389-401.
174. Lee E, Ha S, Logan SK. Divergent androgen receptor and beta-catenin signaling in prostate cancer cells. PLoS One 2015;10:e0141589.
175. Zhang Z, Cheng L, Li J, et al. Inhibition of the Wnt/β-Catenin pathway overcomes resistance to enzalutamide in castration-resistant prostate cancer. Cancer Res 2018;78:3147-62.
176. Takebe N, Miele L, Harris PJ, et al. Targeting Notch, Hedgehog, and Wnt pathways in cancer stem cells: clinical update. Nat Rev Clin Oncol 2015;12:445-64.
177. Zhou HM, Zhang JG, Zhang X, Li Q. Targeting cancer stem cells for reversing therapy resistance: mechanism, signaling, and prospective agents. Signal Transduct Target Ther 2021;6:62.
178. Yeh DW, Huang LR, Chen YW, Huang CF, Chuang TH. Interplay between inflammation and stemness in cancer cells: the role of toll-like receptor signaling. J Immunol Res 2016;2016:4368101.
179. Qin J, Liu Y, Lu Y, et al. Hypoxia-inducible factor 1 alpha promotes cancer stem cells-like properties in human ovarian cancer cells by upregulating SIRT1 expression. Sci Rep 2017;7:10592.
180. Mohiuddin IS, Wei SJ, Kang MH. Role of OCT4 in cancer stem-like cells and chemotherapy resistance. Biochim Biophys Acta Mol Basis Dis 2020;1866:165432.
181. Pires BR, Mencalha AL, Ferreira GM, et al. NF-kappaB is involved in the regulation of EMT genes in breast cancer cells. PLoS One 2017;12:e0169622.
182. Zou K, Li Z, Zhang Y, et al. β-Elemene enhances radiosensitivity in non-small-cell lung cancer by inhibiting epithelial-mesenchymal transition and cancer stem cell traits via Prx-1/NF-kB/iNOS signaling pathway. Aging (Albany NY) 2020;13:2575-92.
183. Li L, Wang T, Hu M, Zhang Y, Chen H, Xu L. Metformin overcomes acquired resistance to EGFR TKIs in EGFR-Mutant lung cancer via AMPK/ERK/NF-κB signaling pathway. Front Oncol 2020;10:1605.
184. Unver N. Macrophage chemoattractants secreted by cancer cells: Sculptors of the tumor microenvironment and another crucial piece of the cancer secretome as a therapeutic target. Cytokine Growth Factor Rev 2019;50:13-8.
185. Hu YB, Yan C, Mu L, et al. Exosomal Wnt-induced dedifferentiation of colorectal cancer cells contributes to chemotherapy resistance. Oncogene 2019;38:1951-65.
186. Bu L, Baba H, Yasuda T, Uchihara T, Ishimoto T. Functional diversity of cancer-associated fibroblasts in modulating drug resistance. Cancer Sci 2020;111:3468-77.
187. Hu JL, Wang W, Lan XL, et al. CAFs secreted exosomes promote metastasis and chemotherapy resistance by enhancing cell stemness and epithelial-mesenchymal transition in colorectal cancer. Mol Cancer 2019;18:91.
188. Lv J, Feng ZP, Chen FK, et al. M2-like tumor-associated macrophages-secreted Wnt1 and Wnt3a promotes dedifferentiation and metastasis via activating β-catenin pathway in thyroid cancer. Mol Carcinog 2021;60:25-37.
189. Chen Y, Tan W, Wang C. Tumor-associated macrophage-derived cytokines enhance cancer stem-like characteristics through epithelial-mesenchymal transition. Onco Targets Ther 2018;11:3817-26.
190. Wang N, Liu W, Zheng Y, et al. CXCL1 derived from tumor-associated macrophages promotes breast cancer metastasis via activating NF-κB/SOX4 signaling. Cell Death Dis 2018;9:880.
191. Zhou K, Cheng T, Zhan J, et al. Targeting tumor-associated macrophages in the tumor microenvironment. Oncol Lett 2020;20:234.
192. Choi CH. ABC transporters as multidrug resistance mechanisms and the development of chemosensitizers for their reversal. Cancer Cell Int 2005;5:30.
193. Nieminen AI, Eskelinen VM, Haikala HM, et al. Myc-induced AMPK-phospho p53 pathway activates Bak to sensitize mitochondrial apoptosis. Proc Natl Acad Sci U S A 2013;110:E1839-48.
194. Sever R, Brugge JS. Signal transduction in cancer. Cold Spring Harb Perspect Med 2015;5:a006098.
196. Pecqueur C, Oliver L, Oizel K, Lalier L, Vallette FM. Targeting metabolism to induce cell death in cancer cells and cancer stem cells. Int J Cell Biol 2013;2013:805975.
197. Heiden MG, Cantley LC, Thompson CB. Understanding the Warburg effect: the metabolic requirements of cell proliferation. Science 2009;324:1029-33.
198. Zhou Y, Tozzi F, Chen J, et al. Intracellular ATP levels are a pivotal determinant of chemoresistance in colon cancer cells. Cancer Res 2012;72:304-14.
199. Soo JS, Ng CH, Tan SH, et al. Metformin synergizes 5-fluorouracil, epirubicin, and cyclophosphamide (FEC) combination therapy through impairing intracellular ATP production and DNA repair in breast cancer stem cells. Apoptosis 2015;20:1373-87.
200. Wang H, Feng Z, Qin Y, Wang J, Xu B. Nucleopeptide assemblies selectively sequester ATP in cancer cells to increase the efficacy of doxorubicin. Angew Chem 2018;130:5025-9.
201. Zheng X, Andruska N, Lambrecht MJ, et al. Targeting multidrug-resistant ovarian cancer through estrogen receptor α dependent ATP depletion caused by hyperactivation of the unfolded protein response. Oncotarget 2018;9:14741-53.
202. Liu G, Wang L, Liu J, et al. Engineering of a core-shell nanoplatform to overcome multidrug resistance via ATP deprivation. Adv Healthc Mater 2020;9:e2000432.
203. Feng LL, Cai YQ, Zhu MC, Xing LJ, Wang X. The yin and yang functions of extracellular ATP and adenosine in tumor immunity. Cancer Cell Int 2020;20:110.
204. Commisso C, Davidson SM, Soydaner-Azeloglu RG, et al. Macropinocytosis of protein is an amino acid supply route in Ras-transformed cells. Nature 2013;497:633-7.
205. Wang H, Gao Z, Liu X, et al. Targeted production of reactive oxygen species in mitochondria to overcome cancer drug resistance. Nat Commun 2018;9:562.
206. Campos-Contreras ADR, Díaz-Muñoz M, Vázquez-Cuevas FG. Purinergic signaling in the hallmarks of cancer. Cells 2020;9:1612.
207. Aroua N, Boet E, Ghisi M, et al. Extracellular ATP and CD39 activate cAMP-mediated mitochondrial stress response to promote cytarabine resistance in acute myeloid leukemia. Cancer Discov 2020;10:1544-65.
208. Li XY, Moesta AK, Xiao C, et al. Targeting CD39 in cancer reveals an extracellular ATP- and inflammasome-driven tumor immunity. Cancer Discov 2019;9:1754-73.
209. Elaskalani O, Falasca M, Moran N, Berndt MC, Metharom P. The role of platelet-derived ADP and ATP in promoting pancreatic cancer cell survival and gemcitabine resistance. Cancers (Basel) 2017;9:142.
210. Virgilio F, Adinolfi E. Extracellular purines, purinergic receptors and tumor growth. Oncogene 2017;36:293-303.
211. Gilbert SM, Oliphant CJ, Hassan S, et al. ATP in the tumour microenvironment drives expression of nfP2X7, a key mediator of cancer cell survival. Oncogene 2019;38:194-208.
212. Arnaud-Sampaio VF, Rabelo ILA, Ulrich H, Lameu C. The P2X7 receptor in the maintenance of cancer stem cells, chemoresistance and metastasis. Stem Cell Rev Rep 2020;16:288-300.
213. Kepp O, Loos F, Liu P, Kroemer G. Extracellular nucleosides and nucleotides as immunomodulators. Immunol Rev 2017;280:83-92.
214. Ghiringhelli F, Apetoh L, Tesniere A, et al. Activation of the NLRP3 inflammasome in dendritic cells induces IL-1beta-dependent adaptive immunity against tumors. Nat Med 2009;15:1170-8.
215. Galluzzi L, Buqué A, Kepp O, Zitvogel L, Kroemer G. Immunogenic cell death in cancer and infectious disease. Nat Rev Immunol 2017;17:97-111.
216. Ohta A. A Metabolic immune checkpoint: adenosine in tumor microenvironment. Front Immunol 2016;7:109.
217. Pietrocola F, Pol J, Kroemer G. Fasting improves anticancer immunosurveillance via autophagy induction in malignant cells. Cell Cycle 2016;15:3327-8.
218. Luo Y, Qiao B, Zhang P, et al. TME-activatable theranostic nanoplatform with ATP burning capability for tumor sensitization and synergistic therapy. Theranostics 2020;10:6987-7001.