Hypoxia inducible factor-1 alpha as a therapeutic target in multiple myeloma

Oncotarget

Volumn 5, Issue 7, 2014, Pages 1779-1792

  Borsi, Enrica ^a   Perrone, Giulia ^b   Terragna, Carolina ^a   Martello, Marina ^a   Dico, Angela F ^a   Solaini, Giancarlo ^a   Baracca, Alessandra ^a   Sgarbi, Gianluca ^a   Pasquinelli, Gianandrea ^a   Valente, Sabrina ^a   Zamagni, Elena ^a   Tacchetti, Paola ^a   Martinelli, Giovanni ^a   Cavo, Michele ^a  

^a UNIVERSITY OF BOLOGNA   (Italy)

^b NATIONAL CANCER INSTITUTE   (Italy)

Author keywords

Cell cycle; HIF 1a; Mitochondria; Multiple myeloma; Warburg effect

Indexed keywords

ADENOSINE TRIPHOSPHATE; ANTINEOPLASTIC AGENT; ANTISENSE OLIGONUCLEOTIDE; CYCLIN A; ENZ 2968; EZN 2968; HYPOXIA INDUCIBLE FACTOR 1ALPHA; MESSENGER RNA; UNCLASSIFIED DRUG; HIF1A PROTEIN, HUMAN; OLIGONUCLEOTIDE; VASCULOTROPIN A;

APOPTOSIS; ARTICLE; CELL CYCLE ARREST; CELL CYCLE S PHASE; CELL METABOLISM; CONTROLLED STUDY; DRUG EFFICACY; DRUG TARGETING; EXPLORATORY RESEARCH; HOMEOSTASIS; HUMAN; HUMAN CELL; MITOCHONDRIAL MEMBRANE POTENTIAL; MULTIPLE MYELOMA; MYELOMA CELL; OXIDATIVE PHOSPHORYLATION; ANTAGONISTS AND INHIBITORS; BIOSYNTHESIS; CELL PROLIFERATION; DOWN REGULATION; DRUG EFFECTS; GENETIC TRANSCRIPTION; GENETICS; METABOLISM; MITOCHONDRION; S PHASE CELL CYCLE CHECKPOINT; TUMOR CELL LINE; ULTRASTRUCTURE;

ADENOSINE TRIPHOSPHATE; APOPTOSIS; CELL LINE, TUMOR; CELL PROLIFERATION; CYCLIN A; DOWN-REGULATION; HUMANS; HYPOXIA-INDUCIBLE FACTOR 1, ALPHA SUBUNIT; MEMBRANE POTENTIAL, MITOCHONDRIAL; MITOCHONDRIA; MULTIPLE MYELOMA; OLIGONUCLEOTIDES; OXIDATIVE PHOSPHORYLATION; RNA, MESSENGER; S PHASE CELL CYCLE CHECKPOINTS; TRANSCRIPTION, GENETIC; VASCULAR ENDOTHELIAL GROWTH FACTOR A;

EID: 84898928636     PISSN: None     EISSN: 19492553     Source Type: Journal    
DOI: 10.18632/oncotarget.1736     Document Type: Article

References (49)

1. Vaupel P. The role of hypoxia-induced factors in tumor progression. Oncologist 2004;9 Suppl 5, 10-7.
2. Semenza GL. Oxygen Sensing, Hypoxia-Inducible Factors, and Disease Pathophysiology. Annu Rev Pathol. 2013 Aug [Epub ahead of print].
3. Wang GL, Jiang BH, Rue EA, Semenza GL. Hypoxiainducible factor 1 is a basic-helix-loop-helix-PAS heterodimer regulated by cellular O2 tension. Proc Natl Acad Sci U S A. 1995;92(12):5510-4.
4. Semenza GL, Wang GL, Kundu R. DNA binding and transcriptional properties of wild-type and mutant forms of the homeodomain protein Msx2. Biochem Biophys Res Commun. 1995;209(1):257-62.
5. Semenza GL. Hypoxia-inducible factor 1 (HIF-1) pathway. Sci STKE 2007;2007(407):cm8. Review.
6. Bristow RG, Hill RP. Hypoxia and metabolism. Hypoxia, DNA repair and genetic instability. Nat Rev Cancer. 2008;8(3):180-92.
7. Theodoropoulos VE, Lazaris AC, Sofras F, Gerzelis I, Tsoukala V, Ghikonti I, Manikas K, Kastriotis I. Hypoxiainducible factor 1 alpha expression correlates with angiogenesis and unfavorable prognosis in bladder cancer. Eur Urol. 2004;46(2):200-8.
8. Yamamoto Y, Ibusuki M, Okumura Y, Kawasoe T, Kai K, Iyama K, Iwase H. Hypoxia-inducible factor 1alpha is closely linked to an aggressive phenotype in breast cancer. Breast Cancer Res Treat. 2008;110(3):465-75.
9. Birner P, Schindl M, Obermair A, Plank C, Breitenecker G, Oberhuber G. Overexpression of hypoxia-inducible factor 1alpha is a marker for an unfavorable prognosis in early-stage invasive cervical cancer. Cancer Res. 2000;60(17):4693-6.
10. Griffiths EA, Pritchard SA, Valentine HR, Whitchelo N, Bishop PW, Ebert MP, Price PM, Welch IM, West CM. Hypoxia-inducible factor-1alpha expression in the gastric carcinogenesis sequence and its prognostic role in gastric and gastro-oesophageal adenocarcinomas. Br J Cancer. 2007;96(1):95-103.
11. Gillies RJ, Gatenby RA. Hypoxia and adaptive landscapes in the evolution of carcinogenesis. Cancer Metastasis Rev. 2007;26(2):311-7.
12. Koshiji M, Kageyama Y, Pete EA, Horikawa I, Barrett JC, Huang LE. HIF-1alpha induces cell cycle arrest by functionally counteracting Myc. EMBO J. 2004;23(9):1949- 56.
13. An WG, Kanekal M, Simon MC, Maltepe E, Blagosklonny MV, Neckers LM. Stabilization of wildtype p53 by hypoxia-inducible factor 1alpha. Nature. 1998;392(6674):405-8.
14. Cam H, Easton JB, High A, Houghton PJ. mTORC1 signaling under hypoxic conditions is controlled by ATM-dependent phosphorylation of HIF-1a. Mol Cell. 2010;40(4):509-20.
15. Kim JW, Gao P, Liu YC, Semenza GL, Dang CV. Hypoxiainducible factor 1 and dysregulated c-Myc cooperatively induce vascular endothelial growth factor and metabolic switches hexokinase 2 and pyruvate dehydrogenase kinase Mol Cell Biol. 2007;27(21):7381-93.
16. Kaufman DS. HIF hits Wnt in the stem cell niche. Nat Cell Biol. 2010;12(10):926-7.
17. Komatsu DE, Hadjiargyrou M. Activation of the transcription factor HIF-1 and its target genes, VEGF, HO-1, iNOS, during fracture repair. Bone. 2004;34(4):680-8.
18. Chan DA, Krieg AJ, Turcotte S, Giaccia AJ. HIF gene expression in cancer therapy. Methods Enzymol. 2007;435:323-45.
19. Winter SC, Shah KA, Han C, Campo L, Turley H, Leek R, Corbridge RJ, Cox GJ, Harris A.L. The relation between hypoxia-inducible factor (HIF)-1alpha and HIF-2alpha expression with anemia and outcome in surgically treated head and neck cancer. Cancer. 2006;107(4):757-66.
20. Ryan HE, Lo J, Johnson RS. HIF-1 alpha is required for solid tumor formation and embryonic vascularization. EMBO J. 1998;17(11):3005-15.
21. Ryan HE, Poloni M, McNulty W, Elson D, Gassmann M, Arbeit JM, Johnson RS. Hypoxia-inducible factor-1alpha is a positive factor in solid tumor growth. Cancer Res. 2000;60(15):4010-5.
22. Liao D, Corle C, Seagroves TN, Johnson RS. Hypoxiainducible factor-1alpha is a key regulator of metastasis in a transgenic model of cancer initiation and progression. Cancer Res. 2007;67(2):563-72.
23. Semenza GL. Evaluation of HIF-1 inhibitors as anticancer agents. Drug Discov Today. 2007;12(19-20):853-9.
24. Colla S, Storti P, Donofrio G, Todoerti K, Bolzoni M, Lazzaretti M, Abeltino M, Ippolito L, Neri A, Ribatti D, Rizzoli V, Martella E, Giuliani N. Low bone marrow oxygen tension and hypoxia-inducible factor- 1a overexpression characterize patients with multiple myeloma: role on the transcriptional and proangiogenic profiles of CD138(+) cells. Leukemia. 2010;24(11):1967- 70.
25. Fujiwara S, Kawano Y, Yuki H, Okuno Y, Nosaka K, Mitsuya H, Hata H. PDK1 inhibition is a novel therapeutic target in multiple myeloma. Br J Cancer. 2013;108(1):170- 8.
26. Blancher C, Moore JW, Robertson N, Harris AL. Effects of ras and von Hippel-Lindau (VHL) gene mutations on hypoxia-inducible factor (HIF)-1alpha, HIF-2alpha, and vascular endothelial growth factor expression and their regulation by the phosphatidylinositol 3'-kinase/Akt signaling pathway. Cancer Res. 2001;61(19):7349-55.
27. Zhang J, Sattler M, Tonon G, Grabher C, Lababidi S, Zimmerhackl A, Raab MS, Vallet S, Zhou Y, Cartron MA, Hideshima T, Tai YT, Chauhan D, Anderson KC, Podar K. Targeting angiogenesis via a c-Myc/hypoxia-inducible factor-1alpha-dependent pathway in multiple myeloma. Cancer Res. 2009;69(12):5082-90.
28. Colla S, Tagliaferri S, Morandi F, Lunghi P, Donofrio G, Martorana D, Mancini C, Lazzaretti M, Mazzera L, Ravanetti L, Bonomini S, Ferrari L, Miranda C, Ladetto M, Neri TM, Neri A, et al. The new tumor-suppressor gene inhibitor of growth family member 4 (ING4) regulates the production of proangiogenic molecules by myeloma cells and suppresses hypoxia-inducible factor-1 alpha (HIF-1alpha) activity: involvement in myeloma-induced angiogenesis. Blood. 2007;110(13):4464-75.
29. Asosingh K, De Raeve H, de Ridder M, Storme GA, Willems A, Van Riet I, Van Camp B, Vanderkerken K. Role of the hypoxic bone marrow microenvironment in 5T2MM murine myeloma tumor progression. Haematologica. 2005;90(6):810-7.
30. Hu Y, Kirito K, Yoshida K, Mitsumori T, Nakajima K, Nozaki Y, Hamanaka S, Nagashima T, Kunitama M, Sakoe K, Komatsu N. Inhibition of hypoxia-inducible factor-1 function enhances the sensitivity of multiple myeloma cells to melphalan. Mol Cancer Ther. 2009;8(8):2329-38.
31. Hu J, Handisides DR, Van Valckenborgh E, De Raeve H, Menu E, Vande Broek I, Liu Q, Sun JD, Van Camp B, Hart CP, Vanderkerken K. Targeting the multiple myeloma hypoxic niche with TH-302, a hypoxia-activated prodrug. Blood. 2010;116(9):1524-7.
32. Storti P, Bolzoni M, Donofrio G, Airoldi I, Guasco D, Toscani D, Martella E, Lazzaretti M, Mancini C, Agnelli L, Patrene K, Maïga S, Franceschi V, Colla S, Anderson J, Neri A, et al. Hypoxia-inducible factor (HIF)-1a suppression in myeloma cells blocks tumoral growth in vivo inhibiting angiogenesis and bone destruction. Leukemia. 2013;27(8):1697-706.
33. Lewis RB, Cohen Y, Nishida HI, Hurwitz C, Arrowwood HE, Uronis F, Gamza F, Longley C, Buchbinder A, Figueroa J. Phase I, pharmacokinetic (PK), dose-escalation study of EZN-2968, a novel hypoxia-inducible factor-1 alpha (HIF-1a) antagonist, administered weekly in patients (pts) with solid tumours. EJC Supplements. 2008;6(12):125.
34. Cohen RB, Olszanski A, Figueroa J, Hurwitz H, Lokiec FM, Rezaï K, Noah B, Aby B. Down-modulation of messenger ribonucleic acid (mRNA) by EZN-2968, an hypoxia-inducible factor-1a (HIF-1a) mRNA antagonist, administered in adult patients with advanced solid tumors [Abstract]. In: Proceeding of the 102nd AACR annual meeting; Orlando, FL; April 5, 2011.
35. Greenberger LM, Horak ID, Filpula D, Sapra P, Westergaard M, Frydenlund HF, Albaek C, Schrøder H, Ørum H. A RNA antagonist of hypoxia-inducible factor- 1alpha, EZN-2968, inhibits tumor cell growth. Mol Cancer Ther. 2008;7(11):3598-608.
36. Lowry O, Rosebrough N, Farr A, Randall R. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951;193(1):265-75.
37. Sgarbi G, Baracca A, Lenaz G, Valentino LM, Carelli V, Solaini G. Inefficient coupling between proton transport and ATP synthesis may be the pathogenic mechanism for NARP and Leigh syndrome resulting from the T8993G mutation in mtDNA. Biochem J. 2006;395(3):493-500.
38. Solaini G, Sgarbi G, Lenaz G, Baracca A. Evaluating mitochondrial membrane potential in cells. Biosci Rep. 2007;27(1-3):11-21.
39. Warburg O. On the origin of cancer cells. Science. 1956;123(3191):309-14.
40. Solaini G, Sgarbi G, Baracca A. Oxidative phosphorylation in cancer cells. Biochim Biophys Acta. 2011;1807(6):534- 42.
41. Chng WJ, Huang GF, Chung TH, Ng SB, Gonzalez-Paz N, Troska-Price T, Mulligan G, Chesi M, Bergsagel PL, Fonseca R. Clinical and biological implications of MYC activation: a common difference between MGUS and newly diagnosed multiple myeloma. Leukemia. 2011;25(6):1026- 35.
42. Podar K, Anderson KC. A therapeutic role for targeting c-Myc/Hif-1-dependent signaling pathways. Cell Cycle. 2010;9(9):1722-8.
43. Elledge SJ. Cell cycle checkpoints: preventing an identity crisis. Science. 1996;274(5293):1664-72.
44. Mazumder S, Gong B, Almasan A. Cyclin E induction by genotoxic stress leads to apoptosis of hematopoietic cells. Oncogene. 2000;19(24):2828-35.
45. Gil-Gómez G, Berns A, Brady HJ. A link between cell cycle and cell death: Bax and Bcl-2 modulate Cdk2 activation during thymocyte apoptosis. EMBO J. 1998;17(24):7209- 18.
46. Culver C, Melvin A, Mudie S, Rocha S. HIF-1a depletion results in SP1-mediated cell cycle disruption and alters the cellular response to chemotherapeutic drugs. Cell Cycle. 2011;10(8):1249-60.
47. Warburg O. On respiratory impairment in cancer cells. Science. 1956;124(3215):269-70.
48. Kim JW, Dang CV. Cancer's molecular sweet tooth and the Warburg effect. Cancer Res. 2006;66(18):8927-30.
49. Baracca A, Sgarbi G, Padula A, Solaini G. Glucose plays a main role in human fibroblasts adaptation to hypoxia. Int J Biochem Cell Biol. 2013;45(7):1356-65.