Copper activates HIF-1α/GPER/VEGF signalling in cancer cells

Oncotarget

Volumn 6, Issue 33, 2015, Pages 34158-34177

  Rigiracciolo, Damiano Cosimo ^a   Scarpelli, Andrea ^a   Lappano, Rosamaria ^a   Pisano, Assunta ^a   Santolla, Maria Francesca ^a   Marco, Paola De ^a   Cirillo, Francesca ^a   Cappello, Anna Rita ^a   Dolce, Vincenza ^a   Belfiore, Antonino ^b   Maggiolini, Marcello ^a   De Francesco, Ernestina Marianna ^a  

^a UNIVERSITY OF CALABRIA   (Italy)

^b UNIVERSITY MAGNA GRAECIA OF CATANZARO   (Italy)

Author keywords

Angiogenesis; Cancer; Copper; GPER; HIF 1 ; Pathology Section; VEGF

Indexed keywords

ACETYLCYSTEINE; CHELATING AGENT; COPPER SULFATE; G PROTEIN COUPLED RECEPTOR 30; HYPOXIA INDUCIBLE FACTOR 1ALPHA; MITOGEN ACTIVATED PROTEIN KINASE; PROTEIN C FOS; TEPA; VASCULOTROPIN; ESTROGEN RECEPTOR; G PROTEIN COUPLED RECEPTOR; GPER PROTEIN, HUMAN; HIF1A PROTEIN, HUMAN; TRANSCRIPTOME; VASCULOTROPIN A; VEGFA PROTEIN, HUMAN;

ANGIOGENESIS; ARTICLE; BREAST CANCER; CANCER CELL LINE; CELL MIGRATION; ENDOTHELIUM CELL; HUMAN; HUMAN CELL; INTRACELLULAR SIGNALING; LIVER CANCER; MOLECULAR MECHANICS; PROTEIN EXPRESSION; PROTEIN FUNCTION; TRANSCRIPTION INITIATION; TUMOR GROWTH; DRUG EFFECTS; FLUORESCENT ANTIBODY TECHNIQUE; METABOLISM; NEOVASCULARIZATION (PATHOLOGY); PHYSIOLOGY; REVERSE TRANSCRIPTION POLYMERASE CHAIN REACTION; SIGNAL TRANSDUCTION; TUMOR CELL LINE; WESTERN BLOTTING;

BLOTTING, WESTERN; CELL LINE, TUMOR; COPPER SULFATE; FLUORESCENT ANTIBODY TECHNIQUE; HUMANS; HYPOXIA-INDUCIBLE FACTOR 1, ALPHA SUBUNIT; NEOVASCULARIZATION, PATHOLOGIC; RECEPTORS, ESTROGEN; RECEPTORS, G-PROTEIN-COUPLED; REVERSE TRANSCRIPTASE POLYMERASE CHAIN REACTION; SIGNAL TRANSDUCTION; TRANSCRIPTOME; VASCULAR ENDOTHELIAL GROWTH FACTOR A;

EID: 84946600617     PISSN: None     EISSN: 19492553     Source Type: Journal    
DOI: 10.18632/oncotarget.5779     Document Type: Article

References (68)

1. Kim BE, Nevitt T, Thiele DJ. Mechanisms for copper acquisition, distribution and regulation. Nat Chem Biol. 2008; 3: 176-185.
2. Georgopoulos PG, Roy A, Yonone-Lioy MJ, Opiekun RE, Lioy PJ. Environmental copper: its dynamics and human exposure issues. J Toxicol Environ Health B Crit Rev. 2001; 4: 341-394.
3. Agency for Toxic Substances and Disease Registry. Toxicological Profile for Copper. Atlanta, GA: US Public Health Service, 1990, p. 43.
4. Rocha GH, Lini RS, Barbosa F Jr, Batista BL, de Oliveira Souza VC, Nerilo SB, Bando E, Mossini SA, Nishiyama P. Exposure to heavy metals due to pesticide use by vineyard farmers. Int Arch Occup Environ Health. 2015; 88:875-80.
5. Antoniades V, Sioga A, Dietrich EM, Meditskou S, Ekonomou L, Antoniades K. Is copper chelation an effective anti-angiogenic strategy for cancer treatment? Med Hypotheses. 2013; 6: 1159-1163.
6. Sabharwal SS, Schumacker PT. Mitochondrial ROS in cancer: initiators, amplifiers or an Achilles' heel? Nat Rev Cancer. 2014; 11: 709-721.
7. Olusi S, Al-Awadhi A, Abiaka C, Abraham M, George S. Serum copper levels and not zinc are positively associated with serum leptin concentrations in the healthy adult population. Biol Trace Elem Res. 2003; 91: 137-144.
8. Gupte A, Mumper RJ. Elevated copper and oxidative stress in cancer cells as a target for cancer treatment. Cancer Treat Rev. 2009; 1: 32-46.
9. Lewis RA, Hultquist DE, Baker BL, Falls HF, Gershowitz H, Penner JA. Hypercupremia associated with a monoclonal immunoglobulin. J Lab Clin Med. 1976; 88: 375-388.
10. Baharvand M, Manifar S, Akkafan R, Mortazavi H, Sabour S. Serum levels of ferritin, copper, and zinc in patients with oral cancer. Biomed J. 2014; 37(5):331-6.
11. Lowndes SA, Harris AL. The role of copper in tumour angiogenesis. J Mammary Gland Biol Neoplasia. 2005; 10: 299-310.
12. Finney L, Vogt S, Fukai T, Glesne D. Copper and angiogenesis: unravelling a relationship key to cancer progression. Clin Exp Pharmacol Physiol. 2009; 36: 88-94.
13. Sen CK, Khanna S, Venojarvi M, Trikha P, Ellison EC, Hunt TK, Roy S. Copper-induced vascular endothelial growth factor expression and wound healing. Am J Physiol Heart Circ Physiol. 2002; 282: H1821-1827.
14. Feng W, Ye F, Xue W, Zhou Z, Kang YJ. Copper regulation of hypoxia-inducible factor-1 activity. Mol Pharmacol. 2009; 1: 174-182.
15. Qiu L, Ding X, Zhang Z, Kang YJ. Copper is required for cobalt-induced transcriptional activity of hypoxia-inducible factor-1. J Pharmacol Exp Ther. 2012; 342: 561-567.
16. Richard DE, Vouret-Craviari V, Pouysségur J. Angiogenesis and G-protein-coupled receptors: signals that bridge the gap. Oncogene. 2001; 20: 1556-1562.
17. De Francesco EM, Lappano R, Santolla MF, Marsico S, Caruso A, Maggiolini M. HIF-1a/GPER signalling mediates the expression of VEGF induced by hypoxia in breast cancer associated fibroblasts (CAFs). Breast Cancer Res. 2013; 15: R64.
18. De Francesco EM, Pellegrino M, Santolla MF, Lappano R, Ricchio E, Abonante S, Maggiolini M. GPER mediates activation of HIF1a/VEGF signalling by estrogens. Cancer Res. 2014; 74: 4053-4064.
19. Martin F, Linden T, Katschinski DM, Oehme F, Flamme I, Mukhopadhyay CK, Eckhardt K, Tröger J, Barth S, Camenisch G, Wenger RH. Copper-dependent activation of hypoxia-inducible factor (HIF)-1: implications for ceruloplasmin regulation. Blood. 2005; 105: 4613-4619.
20. Hu GF. Copper stimulates proliferation of human endothelial cells under culture. J Cell Biochem. 1998; 69: 326-335.
21. Song MO, Li J, Freedman JH. Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009; 38: 386-401.
22. Dong D, Xu X, Wen Y and Kang YJ. Changes in copper concentrations affect the protein levels but not the mRNA levels of copper chaperones in human umbilical vein endothelial cells. Metallomics. 2014; 6: 554-559.
23. Sun, SY. N-acetylcysteine, reactive oxygen species and beyond. Cancer Biol. Ther. 2010; 9: 109-110.
24. Recchia AG, De Francesco EM, Vivacqua A, Sisci D, Panno ML, Andò S, Maggiolini M. The G proteincoupled receptor 30 is up-regulated by hypoxia-inducible factor-1alpha (HIF-1alpha) in breast cancer cells and cardiomyocytes. J Biol Chem. 2011; 286: 10773-10782.
25. Maggiolini M, Vivacqua A, Fasanella G, Recchia AG, Sisci D, Pezzi V, Montanaro D, Musti AM, Picard D, Andò S. The G Protein-coupled Receptor GPR30 Mediates c-fos upregulation by 17b-Estradiol and Phytoestrogens in Breast Cancer Cells. J Biol Chem. 2004; 279: 27008-27016.
26. Maggiolini M, Picard D. The unfolding stories of GPR30, a new membrane-bound estrogen receptor. J Endocrinol. 2010; 204: 105-114.
27. Pandey DP, Lappano R, Albanito L, Madeo A, Maggiolini M, Picard D. Estrogenic GPR30 signalling induces proliferation and migration of breast cancer cells through CTGF. EMBO J. 2009; 28: 523-532.
28. Lappano R, De Marco P, De Francesco EM, Chimento A, Pezzi V, Maggiolini M. Cross-talk between GPER and growth factor signalling. J Steroid Biochem Mol Biol. 2013; 137: 50-56.
29. Staton CA, Reed MW, Brown NJ. A critical analysis of current in vitro and in vivo angiogenesis assays. Int J Exp Pathol. 2009; 90: 195-221.
30. Byzova TV, Goldman CK, Pampori N, Thomas KA, Bett A, Shattil SJ, Plow EF. A mechanism for modulation of cellular responses to VEGF: activation of the integrins. Mol Cell. 2000; 6: 851-860.
31. Morales-Ruiz M, Fulton D, Sowa G, Languino LR, Fujio Y, Walsh K, Sessa WC. Vascular endothelial growth factorstimulated actin reorganization and migration of endothelial cells is regulated via the serine/threonine kinase Akt. Circ Res. 2000; 86: 892-896.
32. Brewer GJ. Anticopper therapy against cancer and diseases of inflammation and fibrosis. Drug Discov Today. 2005; 10: 1103-1119.
33. Ishida S, Andreux P, Poitry-Yamate C, Auwerx J, Hanahan D. Bioavailable copper modulates oxidative phosphorylation and growth of tumors. Proc Natl Acad Sci U S A. 2013; 110: 19507-19512.
34. Wang GL, Semenza GL. General involvement of hypoxiainducible factor 1 in transcriptional response to hypoxia. Proc Natl Acad Sci USA. 1993; 90: 4304-4308.
35. Semenza GL. Hypoxia-inducible factors: mediators of cancer progression and targets for cancer therapy. Trends Pharmacol Sci. 2012; 33: 207-214.
36. Filardo EJ, Graeber CT, Quinn JA, Resnick MB, Giri D, DeLellis RA, Steinhoff MM, Sabo E. Distribution of GPR30, a seven membrane spanning estrogen receptor, in primary breast cancer and its association with clinicopathologic determinants of tumor progression. Clin Cancer Res. 2006; 12: 6359-6366.
37. Smith HO, Leslie KK, Singh M, Qualls CR, Revankar CM, Joste NE, Prossnitz ER. GPR30: a novel indicator of poor survival for endometrial carcinoma. Am J Obstet Gynecol. 2007; 196: 386.e1-9; discussion 386.e9-11.
38. Smith HO, Arias-Pulido H, Kuo DY, Howard T, Qualls CR, Lee SJ, Verschraegen CF, Hathaway HJ, Joste NE, Prossnitz ER. GPR30 predicts poor survival for ovarian cancer. Gynecol Oncol. 2009; 114: 465-471.
39. Vivacqua A, De Marco P, Santolla MF, Cirillo F, Pellegrino M, Panno ML, Abonante S, Maggiolini M. Estrogenic gper signalling regulates mir144 expression in cancer cells and cancer-associated fibroblasts (cafs). Oncotarget. 2015; 6:16573-87. doi: 10.18632/oncotarget.4117.
40. De Marco P, Cirillo F, Vivacqua A, Malaguarnera R, Belfiore A, Maggiolini M. Novel Aspects Concerning the Functional Cross-Talk between the Insulin/IGF-I System and Estrogen Signalling in Cancer Cells. Front Endocrinol (Lausanne). 2015; 6: 30. doi: 10.3389/fendo.2015.00030.
41. Lappano R, Pisano A, Maggiolini M. GPER Function in Breast Cancer: An Overview. Front Endocrinol (Lausanne). 2014; 5: 66. doi: 10.3389/fendo.2014.00066.
42. Santolla MF, De Francesco EM, Lappano R, Rosano C, Abonante S, Maggiolini M. Niacin activates the G protein estrogen receptor (GPER)-mediated signalling. Cell Signal. 2014; 7: 1466-1475.
43. Santolla MF, Lappano R, De Marco P, Pupo M, Vivacqua A, Sisci D, Abonante S, Iacopetta D, Cappello AR, Dolce V, Maggiolini M. G protein-coupled estrogen receptor mediates the up-regulation of fatty acid synthase induced by 17β-estradiol in cancer cells and cancer-associated fibroblasts. J Biol Chem. 2012; 287: 43234-43245.
44. De Francesco EM, Angelone T, Pasqua T, Pupo M, Cerra MC, Maggiolini M. GPER mediates cardiotropic effects in spontaneously hypertensive rat hearts. PLoS One. 2013; 8: e69322.
45. Pupo M, Pisano A, Lappano R, Santolla MF, De Francesco EM, Abonante S, Rosano C, Maggiolini M. Bisphenol A induces gene expression changes and proliferative effects through GPER in breast cancer cells and cancer-associated fibroblasts. Environ Health Perspect. 2012; 120: 1177-1182.
46. Filice E, Angelone T, De Francesco EM, Pellegrino D, Maggiolini M, Cerra MC. Crucial role of phospholamban phosphorylation and S-nitrosylation in the negative lusitropism induced by 17β-estradiol in the male rat heart. Cell Physiol Biochem. 2011; 28: 41-52.
47. Lappano R, Rosano C, De Marco P, De Francesco EM, Pezzi V, Maggiolini M. Estriol acts as a GPR30 antagonist in estrogen receptor-negative breast cancer cells. Mol Cell Endocrinol. 2010; 320: 162-170.
48. Lappano R, Santolla MF, Pupo M, Sinicropi MS, Caruso A, Rosano C, Maggiolini M. MIBE acts as antagonist ligand of both estrogen receptor a and GPER in breast cancer cells. Breast Cancer Res. 2012; 14: R12.
49. Maggiolini M, Santolla MF, Avino S, Aiello F, Rosano C, Garofalo A, Grande F. Identification of two benzopyrroloxazines acting as selective GPER antagonists in breast cancer cells and cancer-associated fibroblasts. Future Med Chem. 2015; 7: 437-448.
50. Sinicropi MS, Lappano R, Caruso A, Santolla MF, Pisano A, Rosano C, Capasso A, Panno A, Lancelot JC, Rault S, Saturnino C, Maggiolini M. (6-bromo-1,4-dimethyl-9Hcarbazol-3-yl-methylene)-hydrazine (carbhydraz) acts as a GPER agonist in breast cancer cells. Curr Top Med Chem. 2015; 15: 1035-42.
51. Bartella V, De Marco P, Malaguarnera R, Belfiore A, Maggiolini M. New advances on the functional cross-talk between insulin-like growth factor-I and estrogen signalling in cancer. Cell Signal. 2012; 24: 1515-1521.
52. De Marco P, Bartella V, Vivacqua A, Lappano R, Santolla MF, Morcavallo A, Pezzi V, Belfiore A, Maggiolini M. Insulin-like growth factor-I regulates GPER expression and function in cancer cells. Oncogene. 2013; 32 :678-688.
53. De Marco P, Romeo E, Vivacqua A, Malaguarnera R, Abonante S, Romeo F, Pezzi V, Belfiore A, Maggiolini M. GPER1 is regulated by insulin in cancer cells and cancerassociated fibroblasts. Endocr Relat Cancer. 2014; 21: 739-753.
54. Santolla MF, Avino S, Pellegrino M, De Francesco EM, De Marco P, Lappano R, Vivacqua A, Cirillo F, Rigiracciolo DC, Scarpelli A, Abonante S and Maggiolini M. SIRT1 is involved in oncogenic signaling mediated by GPER in breast cancer. Cell Death and Disease. 2015 Cdx.doi. org/10.1038/cddis.2015.201.
55. Lappano R, Rosano C, Pisano A, Santolla MF, De Francesco EM, De Marco P, Dolce V, Ponassi M, Felli L, Cafeo G, Kohnke FH, Abonante S, Maggiolini M. A calixpyrrole derivative acts as a GPER antagonist: mechanisms and models. Dis Model Mech. 2015; pii: dmm.021071.
56. Albanito L, Lappano R, Madeo A, Chimento A, Prossnitz ER, Cappello AR, Dolce V, Abonante S, Pezzi V, Maggiolini M. Effects of Atrazine on Estrogen Receptor a-and G Protein-Coupled Receptor 30-Mediated Signalling and Proliferation in Cancer Cells and Cancer-Associated Fibroblasts. Environ Health Perspect. 2015; 123: 493-499.
57. Vivacqua A, Romeo E, De Marco P, De Francesco EM, Abonante S, Maggiolini M. GPER mediates the Egr-1 expression induced by 17β-estradiol and 4-hydroxitamoxifen in breast and endometrial cancer cells. Breast Cancer Res Treat. 2012; 133: 1025-1035.
58. Lappano R, Rosano C, Santolla MF, Pupo M, De Francesco EM, De Marco P, Ponassi M, Spallarossa A, Ranise A, Maggiolini M. Two novel GPER agonists induce gene expression changes and growth effects in cancer cells. Curr Cancer Drug Targets. 2012; 12: 531-542.
59. Lappano R, Maggiolini M. G protein-coupled receptors: novel targets for drug discovery in cancer. Nat Rev Drug Discov. 2011; 10: 47-60.
60. Lappano R, Maggiolini M. GPCRs and cancer. Acta Pharmacol Sin. 2012; 33: 351-362.
61. Madeo A, Maggiolini M. Nuclear alternate estrogen receptor GPR30 mediates 17beta-estradiol-induced gene expression and migration in breast cancer-associated fibroblasts. Cancer Res. 2010; 70: 6036-6046. doi: 10.1158/0008-5472.CAN-10-0408.
62. Pupo M, Pisano A, Abonante S, Maggiolini M, Musti AM. GPER activates Notch signalling in breast cancer cells and cancer-associated fibroblasts (CAFs). Int J Biochem Cell Biol. 2014; 46: 56-67.
63. Pupo M, Vivacqua A, Perrotta I, Pisano A, Aquila S, Abonante S, Gasperi-Campani A, Pezzi V, Maggiolini M. The nuclear localization signal is required for nuclear GPER translocation and function in breast Cancer-Associated Fibroblasts (CAFs). Mol Cell Endocrinol. 2013; 376: 23-32.
64. Martinez-Outschoorn UE, Lisanti MP, Sotgia F. Semin Cancer Biol. Catabolic cancer-associated fibroblasts transfer energy and biomass to anabolic cancer cells, fueling tumor growth. 2014; 25: 47-60.
65. Martinez-Outschoorn U, Sotgia F, Lisanti MP. Tumor microenvironment and metabolic synergy in breast cancers: critical importance of mitochondrial fuels and function. Semin Oncol. 2014; 41: 195-216.
66. Sotgia F, Martinez-Outschoorn UE, Lisanti MP. Cancer metabolism: new validated targets for drug discovery. Oncotarget. 2013; 4: 1309-1316.
67. Yu X, Filardo EJ, Shaikh ZA. The membrane estrogen receptor GPR30 mediates cadmium-induced proliferation of breast cancer cells. Toxicol Appl Pharmacol. 2010; 245: 83-90.
68. Albanito L, Sisci D, Aquila S, Brunelli E, Vivacqua A, Madeo A, Lappano R, Pandey DP, Picard D, Mauro L, Andò S, Maggiolini M. Epidermal growth factor induces G protein-coupled receptor 30 expression in estrogen receptornegative breast cancer. Endocrinology. 2008; 149: 3799-3808.