Na+/H+ exchange in the tumour microenvironment: Does NHE1 drive breast cancer carcinogenesis?

International Journal of Developmental Biology

Volumn 59, Issue 7-8-9, 2015, Pages 367-377

  Amith, Schammim R ^a   Fong, Sunny ^a   Baksh, Shairaz ^a   Fliegel, Larry ^a  

^a UNIVERSITY OF ALBERTA   (Canada)

Author keywords

Breast cancer; Carcinogenesis; Chemotherapy; Metastasis; NHE1

Indexed keywords

BICARBONATE TRANSPORTER; CARIPORIDE; CARRIER PROTEIN; CISPLATIN; CYCLIC AMP DEPENDENT PROTEIN KINASE; DOXORUBICIN; EPIDERMAL GROWTH FACTOR RECEPTOR 2; ESTROGEN RECEPTOR; MESSENGER RNA; MITOGEN ACTIVATED PROTEIN KINASE P38; NERVE CELL ADHESION MOLECULE; PACLITAXEL; PROGESTERONE RECEPTOR; PROTEIN P160; PROTON; PROTON TRANSPORTING ADENOSINE TRIPHOSPHATE SYNTHASE; RHOA GUANINE NUCLEOTIDE BINDING PROTEIN; SODIUM ION; SODIUM PROTON EXCHANGE PROTEIN 1; UNCLASSIFIED DRUG; UVOMORULIN; VIMENTIN; VOLTAGE GATED SODIUM CHANNEL; CATION TRANSPORT PROTEIN; SLC9A1 PROTEIN, HUMAN; SODIUM PROTON EXCHANGE PROTEIN;

ALKALINIZATION; ALLOSTERISM; ARTICLE; BINDING AFFINITY; BINDING KINETICS; BINDING SITE; BREAST CANCER; BREAST CANCER CELL LINE; BREAST CARCINOGENESIS; CANCER CHEMOTHERAPY; CARBOXY TERMINAL SEQUENCE; CELL MEMBRANE; CELL MIGRATION; CELL MOTILITY; CELL PH; CELLULAR ALKALINIZATION; CELLULAR, SUBCELLULAR AND MOLECULAR BIOLOGICAL PHENOMENA AND FUNCTIONS; CYTOSKELETAL REMODELLING; DISEASE ASSOCIATION; DRUG TARGETING; EXTRACELLULAR MATRIX; EXTRACELLULAR PH; HOMEOSTASIS; HUMAN; LIPID BINDING; METASTASIS; MOLECULAR DYNAMICS; NONHUMAN; PH; PHENOTYPE; PODOSOME; PRIORITY JOURNAL; PROTEIN BINDING; PROTEIN DEGRADATION; PROTEIN EXPRESSION; PROTEIN PHOSPHORYLATION; PROTEIN PROTEIN INTERACTION; PROTON TRANSPORT; RISK BENEFIT ANALYSIS; SODIUM TRANSPORT; STRUCTURE ACTIVITY RELATION; TUMOR INVASION; TUMOR MICROENVIRONMENT; ANIMAL; BREAST TUMOR; CARCINOGENESIS; FEMALE; ION TRANSPORT; METABOLISM; PATHOLOGY; PHOSPHORYLATION; PHYSIOLOGY;

ANIMALS; BREAST NEOPLASMS; CARCINOGENESIS; CATION TRANSPORT PROTEINS; FEMALE; HUMANS; ION TRANSPORT; PHOSPHORYLATION; SODIUM-HYDROGEN ANTIPORTER; TUMOR MICROENVIRONMENT;

EID: 84982224385     PISSN: 02146282     EISSN: None     Source Type: Journal    
DOI: 10.1387/ijdb.140336lf     Document Type: Article

References (83)

1. + Exchanger (NHE1) in breast cancer metastasis. Cancer Res 73: 1259-1264.
2. AMITH, S.R., WILKINSON, J.M., BAKSH, S. and FLIEGEL, L. (2015). Na+/H+ exchanger (NHE1) as a novel co-adjuvant target in paclitaxel therapy of triple-negative breast cancer cells. Oncotarget 6: 1262-1275.
3. + exchanger regulation for cardiac protection: a RSKy approach? Curr. Opin. Pharmacol. 8: 133-140.
4. BAUMGARTNER, M., PATEL, H. and BARBER, D.L. (2004). Na(+)/H(+) exchanger NHE1 as plasma membrane scaffold in the assembly of signaling complexes. Am J Physiol Cell Physiol 287: C844-C850.
5. + exchanger isoform 1 (NHE1) is a novel member of the calmodulin-binding proteins. Identification and characterization of calmodulin-binding sites. J Biol Chem 269: 13703-13709.
6. BRACKENBURY, W.J., CHIONI, A.M., DISS, J.K. and DJAMGOZ, M.B. (2007). The neonatal splice variant of Nav1.5 potentiates in vitro invasive behaviour of MDA-MB-231 human breast cancer cells. Breast Cancer Res Treat 101: 149-160.
7. BRISSON, L., DRIFFORT, V., BENOIST, L., POET, M., COUNILLON, L., ANTELMI, E., RUBINO, R., BESSON, P., LABBAL, F., CHEVALIER, S. et al., (2013). NaV1.5 Na(+) channels allosterically regulate the NHE-1 exchanger and promote the activity of breast cancer cell invadopodia. J Cell Sci 126: 4835-4842.
8. BRISSON, L., GILLET, L., CALAGHAN, S., BESSON, P., LE GUENNEC, J.Y., ROGER, S. and GORE, J. (2011). Na(V)1.5 enhances breast cancer cell invasiveness by increasing NHE1-dependent H(+) efflux in caveolae. Oncogene 30: 2070-2076.
9. BUSCO, G., CARDONE, R.A., GRECO, M.R., BELLIZZI, A., COLELLA, M., ANTELMI, E., MANCINI, M.T., DELL’AQUILA, M.E., CASAVOLA, V., PARADISO, A. et al., (2010). NHE1 promotes invadopodial ECM proteolysis through acidification of the peri-invadopodial space. FASEB J 24: 3903-3915.
10. CADOO, K.A., FORNIER, M.N. and MORRIS, P.G. (2013). Biological subtypes of breast cancer: current concepts and implications for recurrence patterns. Q J Nucl Med Mol Imaging 57: 312-321.
11. CARDONE, R.A., BAGORDA, A., BELLIZZI, A., BUSCO, G., GUERRA, L., PARADISO, A., CASAVOLA, V., ZACCOLO, M. and RESHKIN, S.J. (2005a). Protein kinase A gating of a pseudopodial-located RhoA/ROCK/p38/NHE1 signal module regulates invasion in breast cancer cell lines. Mol Biol Cell 16: 3117-3127.
12. + exchanger in metastasis. Nature reviews. Cancer 5: 786-795.
13. CHEUNG, K.J. and EWALD, A.J. (2014). Illuminating breast cancer invasion: diverse roles for cell-cell interactions. Curr Opin Cell Biol 30C: 99-111.
14. DENKER, S.P., HUANG, D.C., ORLOWSKI, J., FURTHMAYR, H. and BARBER, D.L. (2000). Direct binding of the Na-H exchanger NHE1 to ERM proteins regulates the cortical cytoskeleton and cell shape independently of H(+) translocation. Mol Cell 6: 1425-1436.
15. DONOWITZ, M., MING TSE, C. and FUSTER, D. (2013). SLC9/NHE gene family, a plasma membrane and organellar family of Na(+)/H(+) exchangers. Mol Aspects Med 34: 236-251.
16. ELLISON, G., KLINOWSKA, T., WESTWOOD, R.F., DOCTER, E., FRENCH, T. and FOX, J.C. (2002). Further evidence to support the melanocytic origin of MDA-MB-435. Mol Pathol 55: 294-299.
17. FLIEGEL, L. (2009). Regulation of the Na(+)/H(+) exchanger in the healthy and diseased myocardium. Expert Opin Ther Targets 13: 55-68.
18. FRASER, S.P., DISS, J.K., CHIONI, A.M., MYCIELSKA, M.E., PAN, H., YAMACI, R.F., PANI, F., SIWY, Z., KRASOWSKA, M., GRZYWNA, Z. et al., (2005). Voltage-gated sodium channel expression and potentiation of human breast cancer metastasis. Clin Cancer Res 11: 5381-5389.
19. FRASER, S.P., OZERLAT-GUNDUZ, I., BRACKENBURY, W.J., FITZGERALD, E.M., CAMPBELL, T.M., COOMBES, R.C. and DJAMGOZ, M.B. (2014). Regulation of voltage-gated sodium channel expression in cancer: hormones, growth factors and auto-regulation. Philos Trans R Soc Lond B Biol Sci 369: 20130105.
20. FRASER, S.P., SALVADOR, V., MANNING, E.A., MIZAL, J., ALTUN, S., RAZA, M., BERRIDGE, R.J. and DJAMGOZ, M.B. (2003). Contribution of functional voltage-gated Na+ channel expression to cell behaviors involved in the metastatic cascade in rat prostate cancer: I. Lateral motility. J. Cell Physiol. 195: 479-487.
21. FUSTER, D.G. and ALEXANDER, R.T. (2014). Traditional and emerging roles for the SLC9 Na+/H+ exchangers. Pflugers Arch 466: 61-76.
22. GOLDIN, A.L. (2001). Resurgence of sodium channel research. Annu Rev Physiol 63: 871-894.
23. GORBATENKO, A., OLESEN, C.W., BOEDTKJER, E. and PEDERSEN, S.F. (2014). Regulation and roles of bicarbonate transporters in cancer. Front. Physiol. 5: 130.
24. GRECO, M.R., ANTELMI, E., BUSCO, G., GUERRA, L., RUBINO, R., CASAVOLA, V., RESHKIN, S.J. and CARDONE, R.A. (2014). Protease activity at invadopodial focal digestive areas is dependent on NHE1-driven acidic pHe. Oncol Rep 31: 940-946.
25. + exchanger isoform 1 is mediated through phosphorylation of amino acids Ser726 and Ser729. Am J Physiol Cell Physiol 295: C883-C896.
26. HARGUINDEY, S., ARRANZ, J.L., POLO OROZCO, J.D., RAUCH, C., FAIS, S., CARDONE, R.A. and RESHKIN, S.J. (2013). Cariporide and other new and powerful NHE1 inhibitors as potentially selective anticancer drugs--an integral molecular/biochemical/metabolic/clinical approach after one hundred years of cancer research. J Transl Med 11: 282.
27. HASUDA, K., LEE, C. and TANNOCK, I.F. (1994). Antitumor activity of nigericin and 5-(N-ethyl-N-isopropyl)amiloride: an approach to therapy based on cellular acidification and the inhibition of regulation of intracellular pH. Oncology Res. 6: 259-268.
28. HENDUS-ALTENBURGER, R., KRAGELUND, B.B. and PEDERSEN, S.F. (2014). Structural dynamics and regulation of the mammalian SLC9A family of Na(+)/H(+) exchangers. Curr Top Membr 73: 69-148.
29. + exchanger (NHE1): pH-maintenance, ATP-sensitive, and flexible loop domains. J Biochem 121: 295-303.
30. ISAKOFF, S.J. (2010). Triple-negative breast cancer: role of specific chemotherapy agents. Cancer J 16: 53-61.
31. JEON, H.M., KIM DO, H., JUNG, W.H. and KOO, J.S. (2013). Expression of cell metabolism-related genes in different molecular subtypes of triple-negative breast cancer. Tumori 99: 555-564.
32. JUNG, Y.S., KIM, H.Y., KIM, J., LEE, M.G., POUYSSEGUR, J. and KIM, E. (2008). Physical interactions and functional coupling between Daxx and sodium hydrogen exchanger 1 in ischemic cell death. J Biol Chem 283: 1018-1025.
33. KARKI, P., LI, X., SCHRAMA, D. and FLIEGEL, L. (2011). B-RAF is associated with and activates the NHE1 isoform of the Na+/H+ exchanger. J. Biol. Chem. 286: 13096-13105.
34. KARMAZYN, M. (2013). NHE-1: still a viable therapeutic target. J. Molec. Cell. Cardio. 61: 77-82.
35. KAYA, A.O., GUNEL, N., BENEKLI, M., AKYUREK, N., BUYUKBERBER, S., TATLI, H., COSKUN, U., YILDIZ, R., YAMAN, E. and OZTURK, B. (2012). Hypoxia inducible factor-1 alpha and carbonic anhydrase IX overexpression are associated with poor survival in breast cancer patients. J Buon 17: 663-668.
36. 2+. J Biol Chem 286: 40954-40961.
37. LAURITZEN, G., JENSEN, M.B., BOEDTKJER, E., DYBBOE, R., AALKJAER, C., NYLANDSTED, J. and PEDERSEN, S.F. (2010). NBCn1 and NHE1 expression and activity in DeltaNErbB2 receptor-expressing MCF-7 breast cancer cells: contributions to pHi regulation and chemotherapy resistance. Exp Cell Res 316: 2538-2553.
38. LEE, B.L., SYKES, B.D. and FLIEGEL, L. (2013). Structural and functional insights into the cardiac Na(+)/H(+) exchanger. J Mol Cell Cardiol 61: 60-67.
39. + exchange. J Biol Chem 276: 15794-15800.
40. + exchanger. J Biol Chem 277: 36085-36091.
41. LI, X., KHAN, M.F., SCHRIEMER, D.C. and FLIEGEL, L. (2013a). Structural changes in the C-terminal regulatory region of the Na(+)/H(+) exchanger mediate phosphorylation induced regulation. J Mol Cell Cardiol 61: 153-163.
42. LI, X., LIU, Y., ALVAREZ, B.V., CASEY, J.R. and FLIEGEL, L. (2006). A novel carbonic anhydrase II binding site regulates NHE1 activity. Biochemistry 45: 2414-2424.
43. + Exchanger by Ca+2 and Endothelin. Am J Physiol Cell Physiol. C1161-1169.
44. LIU, H., STUPAK, J., ZHENG, J., KELLER, B.O., BRIX, B.J., FLIEGEL, L. and LI, L. (2004). Open tubular immobilized metal-ion affinity chromatography combined with MALDI MS and MS/MS for identification of protein phosphorylation sites. Anal. Chem. 76: 4223-4232.
45. MAGALHAES, M.A., LARSON, D.R., MADER, C.C., BRAVO-CORDERO, J.J., GIL-HENN, H., OSER, M., CHEN, X., KOLESKE, A.J. and CONDEELIS, J. (2011). Cortactin phosphorylation regulates cell invasion through a pH-dependent pathway. J Cell Biol 195: 903-920.
46. 771. J. Biol. Chem. 282: 6292-6299.
47. MARTIN, H.L., SMITH, L. and TOMLINSON, D.C. (2014). Multidrug-resistant breast cancer: current perspectives. Breast Cancer (Dove Med Press) 6: 1-13.
48. MATSUSHITA, M., TANAKA, H., MITSUI, K. and KANAZAWA, H. (2011). Dual functional significance of calcineurin homologous protein 1 binding to Na(+)/H(+) exchanger isoform 1. Am J Physiol Cell Physiol 301: C280-C288.
49. MCCARTY, M.F. and WHITAKER, J. (2010). Manipulating tumor acidification as a cancer treatment strategy. Altern Med Rev 15: 264-272.
50. MEIJER, T.W., BUSSINK, J., ZATOVICOVA, M., SPAN, P.N., LOK, J., SUPURAN, C.T. and KAANDERS, J.H. (2014). Tumor microenvironmental changes induced by the sulfamate carbonic anhydrase IX inhibitor S4 in a laryngeal tumor model. PLoS One 9: e108068.
51. MINCHINTON, A.I. and TANNOCK, I.F. (2006). Drug penetration in solid tumours. Nature Rev. Cancer 6: 583-592.
52. MONTCOURRIER, P., SILVER, I., FARNOUD, R., BIRD, I. and ROCHEFORT, H. (1997). Breast cancer cells have a high capacity to acidify extracellular milieu by a dual mechanism. Clin Exp Metastasis 15: 382-392.
53. MOTAIS, R., COUSIN, J.L. and SOLA, F. (1975). [Transmembrane exchange of C1- and HCO3- in erythrocytes: direct action of carbonic anhydrase inhibitors on the transport mechanism]. C R Acad Sci Hebd Seances Acad Sci D 280: 1119-1122.
54. NERI, D. and SUPURAN, C.T. (2011). Interfering with pH regulation in tumours as a therapeutic strategy. Nat Rev Drug Discov 10: 767-777.
55. ONKAL, R. and DJAMGOZ, M.B. (2009). Molecular pharmacology of voltage-gated sodium channel expression in metastatic disease: clinical potential of neonatal Nav1.5 in breast cancer. Eur. J. Pharmacol. 625: 206-219.
56. PANG, T., WAKABAYASHI, S. and SHIGEKAWA, M. (2002). Expression of calcineurin B homologous protein 2 protects serum deprivation-induced cell death by serum-independent activation of Na+/H+ exchanger. J Biol Chem 277: 43771-43777.
57. PARDO, L.A. and STUHMER, W. (2014). The roles of K(+) channels in cancer. Nat Rev Cancer 14: 39-48.
58. PARIS, S. and POUYSSÉGUR, J. (1984). Growth factor activate the Na+/H+ antiporter in quiescent fibroblasts by increasing its affinity for intracellular H+. J. Biol. Chem. 259: 10989-10994.
59. PARKS, S.K., CHICHE, J. and POUYSSEGUR, J. (2013). Disrupting proton dynamics and energy metabolism for cancer therapy. Nat Rev Cancer 13: 611-623.
60. PEDERSEN, S.F., DARBORG, B.V., RENTSCH, M.L. and RASMUSSEN, M. (2007). Regulation of mitogen-activated protein kinase pathways by the plasma membrane Na+/H+ exchanger, NHE1. Arch Biochem Biophys 462: 195-201.
61. PEDERSEN, S.F. and STOCK, C. (2013). Ion channels and transporters in cancer: pathophysiology, regulation, and clinical potential. Cancer Res 73: 1658-1661.
62. + exchanger, NHE1: structure, regulation, and cellular actions. Annu Rev Pharmacol Toxicol 42: 527-552.
63. RAGHUNAND, N., HE, X., VAN SLUIS, R., MAHONEY, B., BAGGETT, B., TAYLOR, C.W., PAINE-MURRIETA, G., ROE, D., BHUJWALLA, Z.M. and GILLIES, R.J. (1999). Enhancement of chemotherapy by manipulation of tumour pH. Br J Cancer 80: 1005-1011.
64. RESHKIN, S.J., BELLIZZI, A., ALBARANI, V., GUERRA, L., TOMMASINO, M., PARADISO, A. and CASAVOLA, V. (2000a). Phosphoinositide 3-kinase is involved in the tumor-specific activation of human breast cancer cell Na(+)/H(+) exchange, motility, and invasion induced by serum deprivation. J Biol Chem 275: 5361-5369.
65. + exchanger-dependent intracellular alkalinization is an early event in malignant transformation and plays an essential role in the development of subsequent transformation-associated phenotypes. FASEB J 14: 2185-2197.
66. RHODES, D.R., YU, J., SHANKER, K., DESHPANDE, N., VARAMBALLY, R., GHOSH, D., BARRETTE, T., PANDEY, A. and CHINNAIYAN, A.M. (2004). ONCOMINE: a cancer microarray database and integrated data-mining platform. Neoplasia 6: 1-6.
67. 2+ for cancer cell proliferation and survival. Nature Rev. Cancer 8: 361-375.
68. + exchanger 1 is regulated via its lipid-interacting domain, which functions as a molecular switch: a pharmacological approach using indolocarbazole compounds. Mol Pharmacol 85: 18-28.
69. + exchanger 1 is an ATP-binding protein. FEBS J 280: 1430-1442.
70. SLY, W.S. and HU, P.Y. (1995). Human carbonic anhydrases and carbonic anhydrase deficiencies. Annu Rev Biochem 64: 375-401.
71. STOCK, C., CARDONE, R.A., BUSCO, G., KRAHLING, H., SCHWAB, A. and RESHKIN, S.J. (2008). Protons extruded by NHE1: digestive or glue? Eur J Cell Biol 87: 591-599.
72. TAKAHASHI, E., ABE, J., GALLIS, B., AEBERSOLD, R., SPRING, D.J., KREBS, E.G. and BERK, B.C. (1999). p90(RSK) is a serum-stimulated Na+/H+ exchanger isoform-1 kinase. Regulatory phosphorylation of serine 703 of Na+/H+ exchanger isoform-1. J Biol Chem 274: 20206-20214.
73. TAVARES-VALENTE, D., BALTAZAR, F., MOREIRA, R. and QUEIROS, O. (2013). Cancer cell bioenergetics and pH regulation influence breast cancer cell resistance to paclitaxel and doxorubicin. J Bioenerg Biomembr 45: 467-475.
74. VANDER HEIDEN, M.G., CANTLEY, L.C. and THOMPSON, C.B. (2009). Understanding the Warburg effect: the metabolic requirements of cell proliferation. Science 324: 1029-1033.
75. VINCE, J.W. and REITHMEIER, R.A. (1998). Carbonic anhydrase II binds to the carboxyl terminus of human band 3, the erythrocyte C1-/HCO3- exchanger. J Biol Chem 273: 28430-28437.
76. WAKABAYASHI, S., BERTRAND, B., SHIGEKAWA, M., FAFOURNOUX, P. and POUYSSEGUR, J. (1994). Growth factor activation and " H(+)-sensing" of the Na+/H+ exchanger isoform 1 (NHE1). Evidence for an additional mechanism not requiring direct phosphorylation. J Biol Chem 269: 5583-5588.
77. + exchanger NHE1 through sequence-specific interaction. Biochemistry 36: 12854-12861.
78. WAKABAYASHI, S., NAKAMURA, T.Y., KOBAYASHI, S. and HISAMITSU, T. (2010). Novel phorbol ester-binding motif mediates hormonal activation of Na+/H+ exchanger. J Biol Chem 285: 26652-26661.
79. WAKABAYASHI, S., PANG, T., SU, X. and SHIGEKAWA, M. (2000). A novel topology model of the human Na(+)/H(+) exchanger isoform 1. J Biol Chem 275: 7942-7949.
80. + exchangers. Physiol Rev 77: 51-74.
81. WEBB, B.A., CHIMENTI, M., JACOBSON, M.P. and BARBER, D.L. (2011). Dysregulated pH: a perfect storm for cancer progression. Nature reviews. Cancer 11: 671-677.
82. + exchanger recruits ezrin/radixin/moesin proteins to regulate Akt-dependent cell survival. J. Biol. Chem. 279: 26280-26286.
83. ZAUN, H.C., SHRIER, A. and ORLOWSKI, J. (2008). Calcineurin B homologous protein 3 promotes the biosynthetic maturation, cell surface stability, and optimal transport of the Na+/H+ exchanger NHE1 isoform. J Biol Chem 283: 12456-12467.