Hypoxia-inducible factor prolyl hydroxylase 2 (PHD2) is a direct regulator of epidermal growth factor receptor (EGFR) signaling in breast cancer

Oncotarget

Volumn 8, Issue 6, 2017, Pages 9885-9898

  Kozlova, Nina ^a   Wottawa, Marieke ^b   Katschinski, Dörthe Magdalena ^b   Kristiansen, Glen ^c   Kietzmann, Thomas ^a  

^a UNIVERSITY OF OULU   (Finland)

^b UNIVERSITY OF GÖTTINGEN   (Germany)

^c UNIVERSITY HOSPITAL BONN   (Germany)

Author keywords

Breast cancer; EGFR; EGFR signaling; Hypoxia signaling; PHD2

Indexed keywords

EPIDERMAL GROWTH FACTOR RECEPTOR; HYPOXIA INDUCIBLE FACTOR; MITOGEN ACTIVATED PROTEIN KINASE 1; MITOGEN ACTIVATED PROTEIN KINASE 3; PROLYL HYDROXYLASE 2; UNCLASSIFIED DRUG; EGFR PROTEIN, HUMAN; EGLN1 PROTEIN, HUMAN; EPIDERMAL GROWTH FACTOR; HYPOXIA INDUCIBLE FACTOR PROLINE DIOXYGENASE; PROTEIN BINDING;

ADULT; AGED; ARTICLE; BREAST CANCER; BREAST CARCINOGENESIS; CONTROLLED STUDY; CORRELATIONAL STUDY; ENZYME ACTIVATION; HUMAN; HUMAN CELL; HUMAN TISSUE; MAJOR CLINICAL STUDY; MOLECULAR INTERACTION; PROTEIN BINDING; PROTEIN DEGRADATION; PROTEIN EXPRESSION; PROTEIN PROTEIN INTERACTION; PROTEIN STABILITY; SIGNAL TRANSDUCTION; BREAST TUMOR; DRUG EFFECT; ENZYMOLOGY; FEMALE; GENE EXPRESSION REGULATION; GENETIC TRANSFECTION; GENETICS; HEK293 CELL LINE; METABOLISM; PATHOLOGY; PHOSPHORYLATION; RNA INTERFERENCE; TIME FACTOR; TUMOR CELL LINE; TUMOR HYPOXIA; TUMOR MICROENVIRONMENT;

BREAST NEOPLASMS; CELL LINE, TUMOR; EPIDERMAL GROWTH FACTOR; ERBB RECEPTORS; FEMALE; GENE EXPRESSION REGULATION, ENZYMOLOGIC; GENE EXPRESSION REGULATION, NEOPLASTIC; HEK293 CELLS; HUMANS; HYPOXIA-INDUCIBLE FACTOR-PROLINE DIOXYGENASES; PHOSPHORYLATION; PROTEIN BINDING; PROTEIN STABILITY; PROTEOLYSIS; RNA INTERFERENCE; SIGNAL TRANSDUCTION; TIME FACTORS; TRANSFECTION; TUMOR HYPOXIA; TUMOR MICROENVIRONMENT;

EID: 85011966165     PISSN: None     EISSN: 19492553     Source Type: Journal    
DOI: 10.18632/oncotarget.14241     Document Type: Article

References (54)

1. Rimawi MF, Shetty PB, Weiss HL, SchiffR, Osborne CK, Chamness GC, Elledge RM. Epidermal growth factor receptor expression in breast cancer association with biologic phenotype and clinical outcomes. Cancer. 2010; 116: 1234-1242.
2. Bossuyt V, Fadare O, Martel M, Ocal IT, Burtness B, Moinfar F, Leibl S, Tavassoli FA. Remarkably high frequency of EGFR expression in breast carcinomas with squamous differentiation. International Journal of Surgical Pathology. 2005; 13: 319-327.
3. Zhang M, Zhang X, Zhao S, Wang Y, Di W, Zhao G, Yang M, Zhang Q. Prognostic value of survivin and EGFR protein expression in triple-negative breast cancer (TNBC) patients. Targeted Oncology. 2014; 9: 349-357.
4. Masuda H, Zhang D, Bartholomeusz C, Doihara H, Hortobagyi GN, Ueno NT. Role of epidermal growth factor receptor in breast cancer. Breast cancer research and treatment. 2012; 136: 331-345.
5. Irvin Jr. WJ, Carey LA. What is triple-negative breast cancer?. European journal of cancer. 2008; 44: 2799-2805.
6. Shao M, Liu J, Vong JS, Niu Y, Germin B, Tang P, Chan AWH, Lui PCW, Law BKB, Tan P, Tse GM. A subset of breast cancer predisposes to brain metastasis. Medical Molecular Morphology. 2011; 44: 15-20.
7. Zhong H, De Marzo AM, Laughner E, Lim M, Hilton DA, Zagzag D, Buechler P, Isaacs WB, Semenza GL, Simons JW. Overexpression of hypoxia-inducible factor 1a in common human cancers and their metastases. Cancer research. 1999; 59: 5830-5835.
8. Nalwoga H, Ahmed L, Arnes JB, Wabinga H, Akslen LA. Strong expression of hypoxia-inducible factor-1a (HIF-1a) is associated with Axl expression and features of aggressive tumors in African breast cancer. PLoS ONE. 2016; 11: e0146823.
9. Generali D, Fox SB, Berruti A, Brizzi MP, Campo L, Bonardi S, Wigfield SM, Bruzzi P, Bersiga A, Allevi G, Milani M, Aguggini S, Dogliotti L, et al. Role of carbonic anhydrase IX expression in prediction of the efficacy and outcome of primary epirubicin/tamoxifen therapy for breast cancer. Endocrine-related cancer. 2006; 13: 921-930.
10. Liu Z, Semenza GL, Zhang H-. Hypoxia-inducible factor 1 and breast cancer metastasis. Journal of Zhejiang University: Science B. 2015; 16: 32-43.
11. Bos R, Van der Groep P, Greijer AE, Shvarts A, Meijer S, Pinedo HM, Semenza GL, Van Diest PJ, Van der Wall E. Levels of hypoxia-inducible factor-1a independently predict prognosis in patients with lymph node negative breast carcinoma. Cancer. 2003; 97: 1573-1581.
12. Vaupel P, Höckel M, Mayer A. Detection and characterization of tumor hypoxia using pO2 histography. Antioxidants and Redox Signaling. 2007; 9: 1221-1235.
13. Peurala E, Koivunen P, Bloigu R, Haapasaari K, Jukkola-Vuorinen A. Expressions of individual PHDs associate with good prognostic factors and increased proliferation in breast cancer patients. Breast cancer research and treatment. 2012; 133: 179-188.
14. Fox SB, Generali D, Berruti A, Brizzi MP, Campo L, Bonardi S, Bersiga A, Allevi G, Milani M, Aguggini S, Mele T, Dogliotti L, Bottini A, et al. The prolyl hydroxylase enzymes are positively associated with hypoxia-inducible factor-1a and vascular endothelial growth factor in human breast cancer and alter in response to primary systemic treatment with epirubicin and tamoxifen. Breast Cancer Research. 2011; 13: R16.
15. Bordoli MR, Stiehl DP, Borsig L, Kristiansen G, Hausladen S, Schraml P, Wenger RH, Camenisch G. Prolyl-4-hydroxylase PHD2-and hypoxia-inducible factor 2-dependent regulation of amphiregulin contributes to breast tumorigenesis. Oncogene. 2011; 30: 548-560.
16. Franovic A, Gunaratnam L, Smith K, Robert I, Patten D, Lee S. Translational up-regulation of the EGFR by tumor hypoxia provides a nonmutational explanation for its overexpression in human cancer. Proceedings of the National Academy of Sciences of the United States of America. 2007; 104: 13092-13097.
17. Minet E, Arnould T, Michel G, Roland I, Mottet D, Raes M, Remacle J, Michiels C. ERK activation upon hypoxia: Involvement in HIF-1 activation. FEBS letters. 2000; 468: 53-58.
18. Zhong H, Chiles K, Feldser D, Laughner E, Hanrahan C, Georgescu M, Simons JW, Semenza GL. Modulation of hypoxia-inducible factor 1a expression by the epidermal growth factor/phosphatidylinositol 3-kinase/PTEN/AKT/FRAP pathway in human prostate cancer cells: Implications for tumor angiogenesis and therapeutics. Cancer research. 2000; 60: 1541-1545.
19. Laughner E, Taghavi P, Chiles K, Mahon PC, Semenza GL. HER2 (neu) signaling increases the rate of hypoxiainducible factor 1a (HIF-1a) synthesis: Novel mechanism for HIF-1-mediated vascular endothelial growth factor expression. Molecular and cellular biology. 2001; 21: 3995-4004.
20. Semenza GL. Hypoxia-inducible factors in physiology and medicine. Cell. 2012; 148: 399-408.
21. Myllyharju J, Koivunen P. Hypoxia-inducible factor prolyl 4-hydroxylases: common and specific roles. Biological chemistry. 2013; 394: 435-448.
22. Berra E, Benizri E, Ginouvès A, Volmat V, Roux D, Pouysségur J. HIF prolyl-hydroxylase 2 is the key oxygen sensor setting low steady-state levels of HIF-1a in normoxia. EMBO Journal. 2003; 22: 4082-4090.
23. Minder P, Zajac E, Quigley J, Deryugina E. EGFR Regulates the Development and Microarchitecture of Intratumoral Angiogenic Vasculature Capable of Sustaining Cancer Cell Intravasation. Neoplasia. 2015; 17: 634-649.
24. Ueno NT, Zhang D. Targeting EGFR in triple negative breast cancer. Journal of Cancer. 2011; 2: 324-328.
25. Kuchnio A, Moens S, Bruning U, Kuchnio K, Cruys B, Thienpont B, Broux M, Ungureanu AA, de Oliveira RL, Bruyère F, Cuervo H, Manderveld A, Carton A, et al. The cancer cell oxygen sensor PHD2 promotes metastasis via activation of cancer-associated fibroblasts. Cell Reports. 2015; 12: 992-1005.
26. Schofield CJ, Ratcliffe PJ. Oxygen sensing by HIF hydroxylases. Nature Reviews Molecular Cell Biology. 2004; 5: 343-354.
27. Hynes NE, Lane HA. ERBB receptors and cancer: The complexity of targeted inhibitors. Nature Reviews Cancer. 2005; 5: 341-354.
28. Wottawa M, Leisering P, Ahlen MV, Schnelle M, Vogel S, Malz C, Bordoli MR, Camenisch G, Hesse A, Napp J, Alves F, Kristiansen G, Farhat K, et al. Knockdown of prolyl-4-hydroxylase domain 2 inhibits tumor growth of human breast cancer MDA-MB-231 cells by affecting TGF-β1 processing. International Journal of Cancer. 2013; 132: 2787-2798.
29. Samoylenko A, Vynnytska-Myronovska B, Byts N, Kozlova N, Basaraba O, Pasichnyk G, Palyvoda K, Bobak Y, Barska M, Mayevska O, Rzhepetsky Y, Shuvayeva H, Lyzogubov V, et al. Increased levels of the HER1 adaptor protein Rukl/CIN85 contribute to breast cancer malignancy. Carcinogenesis. 2012; 33: 1976-1984.
30. Tomas A, Futter CE, Eden ER. EGF receptor trafficking: Consequences for signaling and cancer. Trends in cell biology. 2014; 24: 26-34.
31. Zhang Q, Yang H. The roles of VHL-dependent ubiquitination in signaling and cancer. Frontiers in Oncology. 2012; 2.
32. De Paulsen N, Brychzy A, Fournier M-, Klausner RD, Gnarra JR, Pause A, Lee S. Role of transforming growth factor-a in von Hippel-Lindau (VHL)-/-clear cell renal carcinoma cell proliferation: A possible mechanism coupling VHL tumor suppressor inactivation and tumorigenesis. Proceedings of the National Academy of Sciences of the United States of America. 2001; 98: 1387-1392.
33. Wang Y, Roche O, Yan MS, Finak G, Evans AJ, Metcalf JL, Hast BE, Hanna SC, Wondergem B, Furge KA, Irwin MS, Kim WY, Teh BT, et al. Regulation of endocytosis via the oxygen-sensing pathway. Nature medicine. 2009; 15: 319-325.
34. Garvalov BK, Foss F, Henze A-, Bethani I, Gräf-Höchst S, Singh D, Filatova A, Dopeso H, Seidel S, Damm M, Acker-Palmer A, Acker T. PHD3 regulates EGFR internalization and signalling in tumours. Nature Communications. 2014; 5: 5577.
35. Gruber G, Greiner RH, Hlushchuk R, Aebersold DM, Altermatt HJ, Berclaz G, Djonov V. Hypoxia-inducible factor 1 alpha in high-risk breast cancer: an independent prognostic parameter?. Breast cancer research: BCR. 2004; 6: R191-198.
36. Kamphues C, Wittschieber D, Klauschen F, Kasajima A, Dietel M, Schmidt S, Glanemann M, Bahra M, Neuhaus P, Weichert W, Stenzinger A. Prolyl hydroxylase domain 2 protein is a strong prognostic marker in human gastric cancer. Pathobiology. 2012; 79: 11-17.
37. Jokilehto T, Rantanen K, Luukkaa M, Heikkinen P, Grenman R, Minn H, Kronqvist P, Jaakkola PM. Overexpression and nuclear translocation of hypoxia-inducible factor prolyl hydroxylase PHD2 in head and neck squamous cell carcinoma is associated with tumor aggressiveness. Clinical Cancer Research. 2006; 12: 1080-1087.
38. Zhen L, Shijie N, Shuijun Z. Tumor PHD2 expression is correlated with clinical features and prognosis of patients with HCC receiving liver resection. Medicine (United States). 2014; 93: e179.
39. Andersen S, Donnem T, Stenvold H, Al-Saad S, Al-Shibli K, Busund L, Bremnes RM. Overexpression of the hif hydroxylases phd1, phd2, phd3 and fih are individually and collectively unfavorable prognosticators for nsclc survival. PLoS ONE. 2011; 6: e23847.
40. Gossage L, Zaitoun A, Fareed KR, Turley H, Aloysius M, Lobo DN, Harris AL, Madhusudan S. Expression of key hypoxia sensing prolyl-hydroxylases PHD1,-2 and-3 in pancreaticobiliary cancer. Histopathology. 2010; 56: 908-920.
41. Herbst JJ, Opresko LK, Walsh BJ, Lauffenburger DA, Wiley HS. Regulation of postendocytic trafficking of the epidermal growth factor receptor through endosomal retention. Journal of Biological Chemistry. 1994; 269: 12865-12873.
42. Slepnev VI, De Camilli P. Accessory factors in clathrindependent synaptic vesicle endocytosis. Nature Reviews Neuroscience. 2000; 1: 161-172.
43. Carey LA, Rugo HS, Marcom PK, Mayer EL, Esteva FJ, Ma CX, Liu MC, Storniolo AM, Rimawi MF, Forero-Torres A, WolffAC, Hobday TJ, Ivanova A, et al. TBCRC 001: Randomized phase II study of cetuximab in combination with carboplatin in stage IV triple-negative breast cancer. Journal of Clinical Oncology. 2012; 30: 2615-2623.
44. Stiehl DP, Bordoli MR, Abreu-Rodríguez I, Wollenick K, Schraml P, Gradin K, Poellinger L, Kristiansen G, Wenger RH. Non-canonical HIF-2a function drives autonomous breast cancer cell growth via an AREG-EGFR/ErbB4 autocrine loop. Oncogene. 2012; 31: 2283-2297.
45. Schmittgen TD, Livak KJ. Analyzing real-time PCR data by the comparative CT method. Nature Protocols. 2008; 3: 1101-1108.
46. Dziadziuszko R, Witta SE, Cappuzzo F, Park S, Tanaka K, Danenberg PV, Barón AE, Crino L, Franklin WA, Bunn Jr. PA, Varella-Garcia M, Danenberg KD, Hirsch FR. Epidermal growth factor receptor messenger RNA expression, gene dosage, and gefitinib sensitivity in nonsmall cell lung cancer. Clinical Cancer Research. 2006; 12: 3078-3084.
47. Galiveti CR, Rozhdestvensky TS, Brosius J, Lehrach H, Konthur Z. Application of housekeeping npcRNAs for quantitative expression analysis of human transcriptome by real-time PCR. RNA. 2010; 16: 450-461.
48. Hsu S-, Hung M. Characterization of a novel tripartite nuclear localization sequence in the EGFR family. Journal of Biological Chemistry. 2007; 282: 10432-10440.
49. Klein A, Flügel D, Kietzmann T. Transcriptional regulation of serine/threonine kinase-15 (STK15) expression by hypoxia and HIF-1. Molecular biology of the cell. 2008; 19: 3667-3675.
50. Scharf J, Unterman TG, Kietzmann T. Oxygen-dependent modulation of insulin-like growth factor binding protein biosynthesis in primary cultures of rat hepatocytes. Endocrinology. 2005; 146: 5433-5443.
51. Kozlova N, Jensen JK, Chi TF, Samoylenko A, Kietzmann T. PAI-1 modulates cell migration in a LRP1-dependent manner via β-catenin and ERK1/2. Thrombosis and haemostasis. 2015; 113: 988-998.
52. Kozlova N, Samoylenko A, Drobot L, Kietzmann T. Urokinase is a negative modulator of Egf-dependent proliferation and motility in the two breast cancer cell lines MCF-7 and MDA-MB-231. Molecular carcinogenesis. 2016; 55: 170-181.
53. Flügel D, Görlach A, Kietzmann T. GSK-3β regulates cell growth, migration, and angiogenesis via Fbw7 and USP28-dependent degradation of HIF-1a. Blood. 2012; 119: 1292-1301.
54. Kozlova N, Wottawa M, Katschinski DM, Kristiansen G, Kietzmann T. Hypoxia inducible factor prolyl hydroxylase 2 (PHD2) is a direct regulator of epidermal growth factor receptor (EGFR) signaling in breast cancer. Annals of Oncology. 2016; 27 (suppl 6).