Chemotherapy triggers HIF-1-dependent glutathione synthesis and copper chelation that induces the breast cancer stem cell phenotype

Proceedings of the National Academy of Sciences of the United States of America

Volumn 112, Issue 33, 2015, Pages E4600-E4609

  Lu, Haiquan ^a   Samanta, Debangshu ^a   Xiang, Lisha ^a   Zhang, Huimin ^a   Hu, Hongxia ^a   Chen, Ivan ^a   Bullen, John W ^a   Semenza, Gregg L ^a  

^a JOHNS HOPKINS UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

Chemotherapy resistance; Hypoxia inducible factor; Paclitaxel; Pluripotency factors; Tumor initiating cells

Indexed keywords

COPPER; GLUTAMATE CYSTEINE LIGASE; GLUTATHIONE; HYPOXIA INDUCIBLE FACTOR 1; MITOGEN ACTIVATED PROTEIN KINASE; PACLITAXEL; TRANSCRIPTION FACTOR FKHRL1; TRANSCRIPTION FACTOR NANOG; ANTINEOPLASTIC AGENT; CHELATING AGENT; HIF1A PROTEIN, HUMAN; HYPOXIA INDUCIBLE FACTOR 1ALPHA; MESSENGER RNA; MITOGEN ACTIVATED PROTEIN KINASE KINASE KINASE; OLIGONUCLEOTIDE;

ARTICLE; CANCER CHEMOTHERAPY; CANCER STEM CELL; CHELATION; CONTROLLED STUDY; COPPER CHELATION; ENZYME INHIBITION; GLUTATHIONE METABOLISM; PRIORITY JOURNAL; PROTEIN EXPRESSION; SIGNAL TRANSDUCTION; TRANSCRIPTION INITIATION; TRIPLE NEGATIVE BREAST CANCER; ANIMAL; CANCER TRANSPLANTATION; CHEMISTRY; CYTOLOGY; FEMALE; GENE EXPRESSION PROFILING; GENE EXPRESSION REGULATION; GENETICS; HUMAN; METABOLISM; MOUSE; PHENOTYPE; PHOSPHORYLATION; SCID MOUSE; TUMOR CELL LINE;

ANIMALS; ANTINEOPLASTIC AGENTS; CELL LINE, TUMOR; CHELATING AGENTS; COPPER; EXTRACELLULAR SIGNAL-REGULATED MAP KINASES; FEMALE; GENE EXPRESSION PROFILING; GENE EXPRESSION REGULATION, NEOPLASTIC; GLUTATHIONE; HUMANS; HYPOXIA-INDUCIBLE FACTOR 1, ALPHA SUBUNIT; MAP KINASE KINASE KINASES; MAP KINASE SIGNALING SYSTEM; MICE; MICE, SCID; NEOPLASM TRANSPLANTATION; NEOPLASTIC STEM CELLS; OLIGONUCLEOTIDES; PACLITAXEL; PHENOTYPE; PHOSPHORYLATION; RNA, MESSENGER; TRIPLE NEGATIVE BREAST NEOPLASMS;

EID: 84939811814     PISSN: 00278424     EISSN: 10916490     Source Type: Journal    
DOI: 10.1073/pnas.1513433112     Document Type: Article

References (52)

1. Foulkes WD, Smith IE, Reis-Filho JS (2010) Triple-negative breast cancer. N Engl J Med 363(20):1938-1948.
2. Dent R, et al. (2007) Triple-negative breast cancer: Clinical features and patterns of recurrence. Clin Cancer Res 13(15 Pt 1):4429-4434.
3. André F, Zielinski CC (2012) Optimal strategies for the treatment of metastatic triple-negative breast cancer with currently approved agents. Ann Oncol 23(Suppl 6):vi46-vi51.
4. Polyak K (2011) Heterogeneity in breast cancer. J Clin Invest 121(10):3786-3788.
5. Pece S, et al. (2010) Biological and molecular heterogeneity of breast cancers correlates with their cancer stem cell content. Cell 140(1):62-73.
6. Oskarsson T, Batlle E, Massagué J (2014) Metastatic stem cells: Sources, niches, and vital pathways. Cell Stem Cell 14(3):306-321.
7. Dean M, Fojo T, Bates S (2005) Tumour stem cells and drug resistance. Nat Rev Cancer 5(4):275-284.
8. Li X, et al. (2008) Intrinsic resistance of tumorigenic breast cancer cells to chemotherapy. J Natl Cancer Inst 100(9):672-679.
9. Bhola NE, et al. (2013) TGF-β inhibition enhances chemotherapy action against triple-negative breast cancer. J Clin Invest 123(3):1348-1358.
10. Samanta D, Gilkes DM, Chaturvedi P, Xiang L, Semenza GL (2014) Hypoxia-inducible factors are required for chemotherapy resistance of breast cancer stem cells. Proc Natl Acad Sci USA 111(50):E5429-E5438.
11. Ginestier C, et al. (2007) ALDH1 is a marker of normal and malignant human mammary stem cells and a predictor of poor clinical outcome. Cell Stem Cell 1(5):555-567.
12. Dontu G, et al. (2003) In vitro propagation and transcriptional profiling of human mammary stem/progenitor cells. Genes Dev 17(10):1253-1270.
13. Vaupel P, Mayer A, Briest S, Höckel M (2005) Hypoxia in breast cancer: Role of blood flow, oxygen diffusion distances, and anemia in the development of oxygen depletion. Adv Exp Med Biol 566:333-342.
14. Semenza GL (2012) Hypoxia-inducible factors in physiology and medicine. Cell 148(3):399-408.
15. Flamant L, Notte A, Ninane N, Raes M, Michiels C (2010) Anti-apoptotic role of HIF-1 and AP-1 in paclitaxel exposed breast cancer cells under hypoxia. Mol Cancer 9:191-205.
16. Suda T, Takubo K, Semenza GL (2011) Metabolic regulation of hematopoietic stem cells in the hypoxic niche. Cell Stem Cell 9(4):298-310.
17. Perales-Clemente E, Folmes CD, Terzic A (2014) Metabolic regulation of redox status in stem cells. Antioxid Redox Signal 21(11):1648-1659.
18. Traverso N, et al. (2013) Role of glutathione in cancer progression and chemoresistance. Oxid Med Cell Longev 2013:972913.
19. Okuno S, et al. (2003) Role of cystine transport in intracellular glutathione level and cisplatin resistance in human ovarian cancer cell lines. Br J Cancer 88(6):951-956.
20. Timmerman LA, et al. (2013) Glutamine sensitivity analysis identifies the xCT anti-porter as a common triple-negative breast tumor therapeutic target. Cancer Cell 24(4):450-465.
21. Harris IS, et al. (2015) Glutathione and thioredoxin antioxidant pathways synergize to drive cancer initiation and progression. Cancer Cell 27(2):211-222.
22. Parker JS, et al. (2009) Supervised risk predictor of breast cancer based on intrinsic subtypes. J Clin Oncol 27(8):1160-1167.
23. Zhang H, et al. (2008) Digoxin and other cardiac glycosides inhibit HIF-1alpha synthesis and block tumor growth. Proc Natl Acad Sci USA 105(50):19579-19586.
24. Sheridan C, et al. (2006) CD44+/CD24- breast cancer cells exhibit enhanced invasive properties: An early step necessary for metastasis. Breast Cancer Res 8(5):R59.
25. Qu Y, et al. (2011) Thioredoxin-like 2 regulates human cancer cell growth and metastasis via redox homeostasis and NF-κB signaling. J Clin Invest 121(1):212-225.
26. Piva M, et al. (2014) Sox2 promotes tamoxifen resistance in breast cancer cells. EMBO Mol Med 6(1):66-79.
27. Cancer Genome Atlas Network (2012) Comprehensive molecular portraits of human breast tumours. Nature 490(7418):61-70.
28. Miyamoto K, et al. (2007) Foxo3a is essential for maintenance of the hematopoietic stem cell pool. Cell Stem Cell 1(1):101-112.
29. Naka K, et al. (2010) TGF-beta-FOXO signalling maintains leukaemia-initiating cells in chronic myeloid leukaemia. Nature 463(7281):676-680.
30. Zhang X, et al. (2011) FOXO1 is an essential regulator of pluripotency in human embryonic stem cells. Nat Cell Biol 13(9):1092-1099.
31. Furuyama T, Nakazawa T, Nakano I, Mori N (2000) Identification of the differential distribution patterns of mRNAs and consensus binding sequences for mouse DAF-16 homologues. Biochem J 349(Pt 2):629-634.
32. Yang JY, et al. (2008) ERK promotes tumorigenesis by inhibiting FOXO3a via MDM2-mediated degradation. Nat Cell Biol 10(2):138-148.
33. Freedman JH, Ciriolo MR, Peisach J (1989) The role of glutathione in copper metabolism and toxicity. J Biol Chem 264(10):5598-5605.
34. Turski ML, et al. (2012) A novel role for copper in Ras/mitogen-activated protein kinase signaling. Mol Cell Biol 32(7):1284-1295.
35. Brady DC, et al. (2014) Copper is required for oncogenic BRAF signalling and tumorigenesis. Nature 509(7501):492-496.
36. Trachootham D, et al. (2006) Selective killing of oncogenically transformed cells through a ROS-mediated mechanism by beta-phenylethyl isothiocyanate. Cancer Cell 10(3):241-252.
37. Balendiran GK, Dabur R, Fraser D (2004) The role of glutathione in cancer. Cell Biochem Funct 22(6):343-352.
38. Lo M, Ling V, Wang YZ, Gout PW (2008) The xc- cystine/glutamate antiporter: A mediator of pancreatic cancer growth with a role in drug resistance. Br J Cancer 99(3):464-472.
39. Narang VS, Pauletti GM, Gout PW, Buckley DJ, Buckley AR (2007) Sulfasalazine-induced reduction of glutathione levels in breast cancer cells: Enhancement of growth-inhibitory activity of Doxorubicin. Chemotherapy 53(3):210-217.
40. Sullivan LB, et al. (2013) The proto-oncometabolite fumarate binds glutathione to amplify ROS-dependent signaling. Mol Cell 51(2):236-248.
41. Kim BE, Nevitt T, Thiele DJ (2008) Mechanisms for copper acquisition, distribution and regulation. Nat Chem Biol 4(3):176-185.
42. Gupte A, Mumper RJ (2009) Elevated copper and oxidative stress in cancer cells as a target for cancer treatment. Cancer Treat Rev 35(1):32-46.
43. Ishida S, Andreux P, Poitry-Yamate C, Auwerx J, Hanahan D (2013) Bioavailable copper modulates oxidative phosphorylation and growth of tumors. Proc Natl Acad Sci USA 110(48):19507-19512.
44. Juarez JC, et al. (2006) Copper binding by tetrathiomolybdate attenuates angiogenesis and tumor cell proliferation through the inhibition of superoxide dismutase 1. Clin Cancer Res 12(16):4974-4982.
45. Booth A, Trudeau T, Gomez C, Lucia MS, Gutierrez-Hartmann A (2014) Persistent ERK/ MAPK activation promotes lactotrope differentiation and diminishes tumorigenic phenotype. Mol Endocrinol 28(12):1999-2011.
46. Burdon T, Smith A, Savatier P (2002) Signalling, cell cycle and pluripotency in embryonic stem cells. Trends Cell Biol 12(9):432-438.
47. Hamilton WB, Brickman JM (2014) Erk signaling suppresses embryonic stem cell self-renewal to specify endoderm. Cell Reports 9(6):2056-2070.
48. Leitch HG, et al. (2010) Embryonic germ cells from mice and rats exhibit properties consistent with a generic pluripotent ground state. Development 137(14):2279-2287.
49. Eijkelenboom A, Burgering BM (2013) FOXOs: Signalling integrators for homeostasis maintenance. Nat Rev Mol Cell Biol 14(2):83-97.
50. Zhang H, et al. (2012) HIF-1-dependent expression of angiopoietin-like 4 and L1CAM mediates vascular metastasis of hypoxic breast cancer cells to the lungs. Oncogene 31(14):1757-1770.
51. Xiang L, et al. (2014) Ganetespib blocks HIF-1 activity and inhibits tumor growth, vascularization, stem cell maintenance, invasion, and metastasis in orthotopic mouse models of triple-negative breast cancer. J Mol Med (Berl) 92(2):151-164.
52. Semenza GL (2015) The hypoxic tumor microenvironment: A driving force for breast cancer progression. Biochim Biophys Acta pii:S0167-4889(15):00192-00195.