Calcium sensing receptor signalling in physiology and cancer

Biochimica et Biophysica Acta - Molecular Cell Research

Volumn 1833, Issue 7, 2013, Pages 1732-1744

  Brennan, Sarah C ^a,b   Thiem, Ursula ^a,c   Roth, Susanne ^a,d   Aggarwal, Abhishek ^a,e   Fetahu, Irfete Sh ^a,e   Tennakoon, Samawansha ^a,e   Gomes, Ana Rita ^a,f   Brandi, Maria Luisa ^a,f   Bruggeman, Frank ^a,d   Mentaverri, Romuald ^a,c   Riccardi, Daniela ^a,b   Kallay, Enikö ^a,e  

^a Multifaceted CaSR Initial Training Network   (United Kingdom)

^b CARDIFF UNIVERSITY   (United Kingdom)

^c INSERM   (France)

^d VU UNIVERSITY AMSTERDAM   (Netherlands)

^e MEDICAL UNIVERSITY OF VIENNA   (Austria)

^f UNIVERSITY OF FLORENCE   (Italy)

Author keywords

Breast cancer; Colorectal cancer; Ligand biased signalling; Parathyroid adenoma; Prostate cancer; Systems biology

Indexed keywords

CALCIUM ION; CALCIUM SENSING RECEPTOR; CYTOCHROME P450; FILAMIN A; MITOGEN ACTIVATED PROTEIN KINASE; MITOGEN ACTIVATED PROTEIN KINASE P38; PARATHYROID HORMONE RELATED PROTEIN; PROSTAGLANDIN SYNTHASE; PROTEIN KINASE C;

ARTICLE; BONE METASTASIS; BREAST CANCER; CALCIUM SIGNALING; CANCER INHIBITION; CARCINOGENESIS; CELL MIGRATION; CELL PROLIFERATION; COLORECTAL CANCER; DISEASE ASSOCIATION; ENZYME ACTIVATION; ENZYME PHOSPHORYLATION; HOMEOSTASIS; INTESTINE MOTILITY; NEOPLASM; NONHUMAN; PARATHYROID TUMOR; PHYSIOLOGY; PRIORITY JOURNAL; PROSTATE CANCER; PROTEIN EXPRESSION; RECEPTOR BINDING; SIGNAL TRANSDUCTION;

ANIMALS; ANTINEOPLASTIC AGENTS; CALCIUM; HUMANS; NEOPLASMS; RECEPTORS, CALCIUM-SENSING; SIGNAL TRANSDUCTION;

EID: 84878251423     PISSN: 01674889     EISSN: 18792596     Source Type: Journal    
DOI: 10.1016/j.bbamcr.2012.12.011     Document Type: Article

References (182)

1. Brown E.M., MacLeod R.J. Extracellular calcium sensing and extracellular calcium signaling. Physiol. Rev. 2001, 81:239-297.
2. Conigrave A.D., Brown E.M. Taste receptors in the gastrointestinal tract. II. L-amino acid sensing by calcium-sensing receptors: implications for GI physiology. Am. J. Physiol. Gastrointest. Liver Physiol. 2006, 291:G753-G761.
3. Brown E.M., Gamba G., Riccardi D., Lombardi M., Butters R., Kifor O., Sun A., Hediger M.A., Lytton J., Hebert S.C. Cloning and characterization of an extracellular Ca(2+)-sensing receptor from bovine parathyroid. Nature 1993, 366:575-580.
4. Wettschureck N., Lee E., Libutti S.K., Offermanns S., Robey P.G., Spiegel A.M. Parathyroid-specific double knockout of Gq and G11 alpha-subunits leads to a phenotype resembling germline knockout of the extracellular Ca2+-sensing receptor. Mol. Endocrinol. 2007, 21:274-280.
5. Ho C., Conner D.A., Pollak M.R., Ladd D.J., Kifor O., Warren H.B., Brown E.M., Seidman J.G., Seidman C.E. A mouse model of human familial hypocalciuric hypercalcemia and neonatal severe hyperparathyroidism. Nat. Genet. 1995, 11:389-394.
6. Marx S.J., Lasker R.D., Brown E.M., Fitzpatrick L.A., Sweezey N.B., Goldbloom R.B., Gillis D.A., Cole D.E. Secretory dysfunction in parathyroid cells from a neonate with severe primary hyperparathyroidism. J. Clin. Endocrinol. Metab. 1986, 62:445-449.
7. Hendy G.N., Guarnieri V., Canaff L. Calcium-sensing receptor and associated diseases. Prog. Mol. Biol. Transl. Sci. 2009, 89:31-95.
8. Cheng S.X., Okuda M., Hall A.E., Geibel J.P., Hebert S.C. Expression of calcium-sensing receptor in rat colonic epithelium: evidence for modulation of fluid secretion. Am. J. Physiol. Gastrointest. Liver Physiol. 2002, 283:G240-G250.
9. Geibel J., Sritharan K., Geibel R., Geibel P., Persing J.S., Seeger A., Roepke T.K., Deichstetter M., Prinz C., Cheng S.X., Martin D., Hebert S.C. Calcium-sensing receptor abrogates secretagogue-induced increases in intestinal net fluid secretion by enhancing cyclic nucleotide destruction. Proc. Natl. Acad. Sci. U. S. A. 2006, 103:9390-9397.
10. Chattopadhyay N., Cheng I., Rogers K., Riccardi D., Hall A., Diaz R., Hebert S.C., Soybel D.I., Brown E.M. Identification and localization of extracellular Ca(2+)-sensing receptor in rat intestine. Am. J. Physiol. 1998, 274:G122-G130.
11. Rey O., Young S.H., Jacamo R., Moyer M.P., Rozengurt E. Extracellular calcium sensing receptor stimulation in human colonic epithelial cells induces intracellular calcium oscillations and proliferation inhibition. J. Cell. Physiol. 2010, 225:73-83.
12. Breitwieser G.E. Calcium sensing receptors and calcium oscillations: calcium as a first messenger. Curr. Top. Dev. Biol. 2006, 73:85-114.
13. Miki H., Maercklein P.B., Fitzpatrick L.A. Spontaneous oscillations of intracellular calcium in single bovine parathyroid cells may be associated with the inhibition of parathyroid hormone secretion. Endocrinology 1995, 136:2954-2959.
14. Ridefelt P., Bjorklund E., Akerstrom G., Olsson M.J., Rastad J., Gylfe E. Ca(2+)-induced Ca2+ oscillations in parathyroid cells. Biochem. Biophys. Res. Commun. 1995, 215:903-909.
15. Breitwieser G.E., Gama L. Calcium-sensing receptor activation induces intracellular calcium oscillations. Am. J. Physiol. Cell Physiol. 2001, 280:C1412-C1421.
16. Szekely D., Brennan S.C., Mun H.C., Conigrave A.D., Kuchel P.W. Effectors of the frequency of calcium oscillations in HEK-293 cells: wavelet analysis and a computer model. Eur. Biophys. J. 2009, 39:149-165.
17. Young S.H., Rozengurt E. Amino acids and Ca2+ stimulate different patterns of Ca2+ oscillations through the Ca2+-sensing receptor. Am. J. Physiol. Cell Physiol. 2002, 282:C1414-C1422.
18. Young S.H., Wu S.V., Rozengurt E. Ca2+-stimulated Ca2+ oscillations produced by the Ca2+-sensing receptor require negative feedback by protein kinase C. J. Biol. Chem. 2002, 277:46871-46876.
19. Davies S.L., Ozawa A., McCormick W.D., Dvorak M.M., Ward D.T. Protein kinase C-mediated phosphorylation of the calcium-sensing receptor is stimulated by receptor activation and attenuated by calyculin-sensitive phosphatase activity. J. Biol. Chem. 2007, 282:15048-15056.
20. McCormick W.D., Atkinson-Dell R., Campion K.L., Mun H.C., Conigrave A.D., Ward D.T. Increased receptor stimulation elicits differential calcium-sensing receptor (T888) dephosphorylation. J. Biol. Chem. 2010, 285:14170-14177.
21. Bai M., Trivedi S., Lane C.R., Yang Y., Quinn S.J., Brown E.M. Protein kinase C phosphorylation of threonine at position 888 in Ca2+o-sensing receptor (CaR) inhibits coupling to Ca2+ store release. J. Biol. Chem. 1998, 273:21267-21275.
22. Jiang Y.F., Zhang Z., Kifor O., Lane C.R., Quinn S.J., Bai M. Protein kinase C (PKC) phosphorylation of the Ca2+ o-sensing receptor (CaR) modulates functional interaction of G proteins with the CaR cytoplasmic tail. J. Biol. Chem. 2002, 277:50543-50549.
23. Lazarus S., Pretorius C.J., Khafagi F., Campion K.L., Brennan S.C., Conigrave A.D., Brown E.M., Ward D.T. A novel mutation of the primary protein kinase C phosphorylation site in the calcium-sensing receptor causes autosomal dominant hypocalcemia. Eur. J. Endocrinol. 2011, 164:429-435.
24. Freichel M., Zink-Lorenz A., Holloschi A., Hafner M., Flockerzi V., Raue F. Expression of a calcium-sensing receptor in a human medullary thyroid carcinoma cell line and its contribution to calcitonin secretion. Endocrinology 1996, 137:3842-3848.
25. Ferreri N.R., Hao S., Pedraza P.L., Escalante B., Vio C.P. Eicosanoids and tumor necrosis factor-alpha in the kidney. Prostaglandins Other Lipid Mediat. 2012, 98:101-106.
26. Hobson S.A., McNeil S.E., Lee F., Rodland K.D. Signal transduction mechanisms linking increased extracellular calcium to proliferation in ovarian surface epithelial cells. Exp. Cell Res. 2000, 258:1-11.
27. Handlogten M.E., Huang C., Shiraishi N., Awata H., Miller R.T. The Ca2+-sensing receptor activates cytosolic phospholipase A2 via a Gqalpha-dependent ERK-independent pathway. J. Biol. Chem. 2001, 276:13941-13948.
28. Kifor O., MacLeod R.J., Diaz R., Bai M., Yamaguchi T., Yao T., Kifor I., Brown E.M. Regulation of MAP kinase by calcium-sensing receptor in bovine parathyroid and CaR-transfected HEK293 cells. Am. J. Physiol. Renal Physiol. 2001, 280:F291-F302.
29. Holstein D.M., Berg K.A., Leeb-Lundberg L.M., Olson M.S., Saunders C. Calcium-sensing receptor-mediated ERK1/2 activation requires Galphai2 coupling and dynamin-independent receptor internalization. J. Biol. Chem. 2004, 279:10060-10069.
30. Lee H.J., Mun H.C., Lewis N.C., Crouch M.F., Culverston E.L., Mason R.S., Conigrave A.D. Allosteric activation of the extracellular Ca2+-sensing receptor by L-amino acids enhances ERK1/2 phosphorylation. Biochem. J. 2007, 404:141-149.
31. MacLeod R.J., Yano S., Chattopadhyay N., Brown E.M. Extracellular calcium-sensing receptor transactivates the epidermal growth factor receptor by a triple-membrane-spanning signaling mechanism. Biochem. Biophys. Res. Commun. 2004, 320:455-460.
32. Saidak Z., Mentaverri R., Brown E.M. The role of the calcium-sensing receptor in the development and progression of cancer. Endocr. Rev. 2009, 30:178-195.
33. Casala C., Gil-Guinon E., Ordonez J.L., Miguel-Queralt S., Rodriguez E., Galvan P., Lavarino C., Munell F., de Alava E., Mora J., de Torres C. The calcium-sensing receptor is silenced by genetic and epigenetic mechanisms in unfavorable neuroblastomas and its reactivation induces ERK1/2-dependent apoptosis. Carcinogenesis 2012.
34. Mamillapalli R., VanHouten J., Zawalich W., Wysolmerski J. Switching of G-protein usage by the calcium-sensing receptor reverses its effect on parathyroid hormone-related protein secretion in normal versus malignant breast cells. J. Biol. Chem. 2008, 283:24435-24447.
35. Huang C., Hydo L.M., Liu S., Miller R.T. Activation of choline kinase by extracellular Ca2+ is Ca(2+)-sensing receptor, Galpha12 and Rho-dependent in breast cancer cells. Cell. Signal. 2009, 21:1894-1900.
36. Worzfeld T., Wettschureck N., Offermanns S. G(12)/G(13)-mediated signalling in mammalian physiology and disease. Trends Pharmacol. Sci. 2008, 29:582-589.
37. Ward D.T., Riccardi D. New concepts in calcium-sensing receptor pharmacology and signalling. Br. J. Pharmacol. 2012, 165:35-48.
38. Bilezikian J.P., Silverberg S.J. Clinical spectrum of primary hyperparathyroidism. Rev. Endocr. Metab. Disord. 2000, 1:237-245.
39. Wei C.H., Harari A. Parathyroid carcinoma: update and guidelines for management. Curr. Treat. Options Oncol. 2012, 13:11-23.
40. Corbetta S., Mantovani G., Lania A., Borgato S., Vicentini L., Beretta E., Faglia G., Di Blasio A.M., Spada A. Calcium-sensing receptor expression and signalling in human parathyroid adenomas and primary hyperplasia. Clin. Endocrinol. (Oxf) 2000, 52:339-348.
41. Gogusev J., Duchambon P., Hory B., Giovannini M., Goureau Y., Sarfati E., Drueke T.B. Depressed expression of calcium receptor in parathyroid gland tissue of patients with hyperparathyroidism. Kidney Int. 1997, 51:328-336.
42. Farnebo F., Enberg U., Grimelius L., Backdahl M., Schalling M., Larsson C., Farnebo L.O. Tumor-specific decreased expression of calcium sensing receptor messenger ribonucleic acid in sporadic primary hyperparathyroidism. J. Clin. Endocrinol. Metab. 1997, 82:3481-3486.
43. Haven C.J., van Puijenbroek M., Karperien M., Fleuren G.J., Morreau H. Differential expression of the calcium sensing receptor and combined loss of chromosomes 1q and 11q in parathyroid carcinoma. J. Pathol. 2004, 202:86-94.
44. Cetani F., Pinchera A., Pardi E., Cianferotti L., Vignali E., Picone A., Miccoli P., Viacava P., Marcocci C. No evidence for mutations in the calcium-sensing receptor gene in sporadic parathyroid adenomas. J. Bone Miner. Res. 1999, 14:878-882.
45. Yano S., Sugimoto T., Tsukamoto T., Chihara K., Kobayashi A., Kitazawa S., Maeda S., Kitazawa R. Association of decreased calcium-sensing receptor expression with proliferation of parathyroid cells in secondary hyperparathyroidism. Kidney Int. 2000, 58:1980-1986.
46. Miller G., Davis J., Shatzen E., Colloton M., Martin D., Henley C.M. Cinacalcet HCl prevents development of parathyroid gland hyperplasia and reverses established parathyroid gland hyperplasia in a rodent model of CKD. Nephrol. Dial. Transplant. 2012, 27:2198-2205.
47. Mizobuchi M., Hatamura I., Ogata H., Saji F., Uda S., Shiizaki K., Sakaguchi T., Negi S., Kinugasa E., Koshikawa S., Akizawa T. Calcimimetic compound upregulates decreased calcium-sensing receptor expression level in parathyroid glands of rats with chronic renal insufficiency. J. Am. Soc. Nephrol. 2004, 15:2579-2587.
48. Mendoza F.J., Lopez I., Canalejo R., Almaden Y., Martin D., Aguilera-Tejero E., Rodriguez M. Direct upregulation of parathyroid calcium-sensing receptor and vitamin D receptor by calcimimetics in uremic rats. Am. J. Physiol. Renal Physiol. 2009, 296:F605-F613.
49. Koh J., Dar M., Untch B.R., Dixit D., Shi Y., Yang Z., Adam M.A., Dressman H., Wang X., Gesty-Palmer D., Marks J.R., Spurney R., Druey K.M., Olson J.A. Regulator of G protein signaling 5 is highly expressed in parathyroid tumors and inhibits signaling by the calcium-sensing receptor. Mol. Endocrinol. 2011, 25:867-876.
50. Imanishi Y., Hosokawa Y., Yoshimoto K., Schipani E., Mallya S., Papanikolaou A., Kifor O., Tokura T., Sablosky M., Ledgard F., Gronowicz G., Wang T.C., Schmidt E.V., Hall C., Brown E.M., Bronson R., Arnold A. Primary hyperparathyroidism caused by parathyroid-targeted overexpression of cyclin D1 in transgenic mice. J. Clin. Invest. 2001, 107:1093-1102.
51. Mallya S.M., Arnold A. Cyclin D1 in parathyroid disease. Front. Biosci. 2000, 5:D367-D371.
52. Bjorklund P., Akerstrom G., Westin G. Activated beta-catenin in the novel human parathyroid tumor cell line sHPT-1. Biochem. Biophys. Res. Commun. 2007, 352:532-536.
53. Corbetta S., Eller-Vainicher C., Vicentini L., Lania A., Mantovani G., Beck-Peccoz P., Spada A. Modulation of cyclin D1 expression in human tumoral parathyroid cells: effects of growth factors and calcium sensing receptor activation. Cancer Lett. 2007, 255:34-41.
54. Mallya S.M., Gallagher J.J., Wild Y.K., Kifor O., Costa-Guda J., Saucier K., Brown E.M., Arnold A. Abnormal parathyroid cell proliferation precedes biochemical abnormalities in a mouse model of primary hyperparathyroidism. Mol. Endocrinol. 2005, 19:2603-2609.
55. Kifor O., Kifor I., Moore F.D., Butters R.R., Cantor T., Gao P., Brown E.M. Decreased expression of caveolin-1 and altered regulation of mitogen-activated protein kinase in cultured bovine parathyroid cells and human parathyroid adenomas. J. Clin. Endocrinol. Metab. 2003, 88:4455-4464.
56. Corbetta S., Lania A., Filopanti M., Vicentini L., Ballare E., Spada A. Mitogen-activated protein kinase cascade in human normal and tumoral parathyroid cells. J. Clin. Endocrinol. Metab. 2002, 87:2201-2205.
57. Parkin D.M., Bray F., Ferlay J., Pisani P. Global cancer statistics, 2002. CA Cancer J. Clin. 2005, 55:74-108.
58. Center M.M., Jemal A., Smith R.A., Ward E. Worldwide variations in colorectal cancer. CA Cancer J. Clin. 2009, 59:366-378.
59. Garland C., Shekelle R.B., Barrett-Connor E., Criqui M.H., Rossof A.H., Paul O. Dietary vitamin D and calcium and risk of colorectal cancer: a 19-year prospective study in men. Lancet 1985, 1:307-309.
60. Van der Meer R., De Vries H.T. Differential binding of glycine- and taurine-conjugated bile acids to insoluble calcium phosphate. Biochem. J. 1985, 229:265-268.
61. Newmark H.L., Wargovich M.J., Bruce W.R. Colon cancer and dietary fat, phosphate, and calcium: a hypothesis. J. Natl. Cancer Inst. 1984, 72:1323-1325.
62. Fedirko V., Bostick R.M., Flanders W.D., Long Q., Sidelnikov E., Shaukat A., Daniel C.R., Rutherford R.E., Woodard J.J. Effects of vitamin d and calcium on proliferation and differentiation in normal colon mucosa: a randomized clinical trial. Cancer Epidemiol. Biomarkers Prev. 2009, 18:2933-2941.
63. Fedirko V., Bostick R.M., Flanders W.D., Long Q., Shaukat A., Rutherford R.E., Daniel C.R., Cohen V., Dash C. Effects of vitamin D and calcium supplementation on markers of apoptosis in normal colon mucosa: a randomized, double-blind, placebo-controlled clinical trial. Cancer Prev. Res. (Phila.) 2009, 2:213-223.
64. Lipkin M., Newmark H. Effect of added dietary calcium on colonic epithelial-cell proliferation in subjects at high risk for familial colonic cancer. N. Engl. J. Med. 1985, 313:1381-1384.
65. Kallay E., Kifor O., Chattopadhyay N., Brown E.M., Bischof M.G., Peterlik M., Cross H.S. Calcium-dependent c-myc proto-oncogene expression and proliferation of Caco-2 cells: a role for a luminal extracellular calcium-sensing receptor. Biochem. Biophys. Res. Commun. 1997, 232:80-83.
66. Kallay E., Bajna E., Wrba F., Kriwanek S., Peterlik M., Cross H.S. Dietary calcium and growth modulation of human colon cancer cells: role of the extracellular calcium-sensing receptor. Cancer Detect. Prev. 2000, 24:127-136.
67. Rey O., Chang W., Bikle D., Rozengurt N., Young S.H., Rozengurt E. Negative cross-talk between calcium-sensing receptor and beta-catenin signaling systems in colonic epithelium. J. Biol. Chem. 2012, 287:1158-1167.
68. Ahearn T.U., McCullough M.L., Flanders W.D., Long Q., Sidelnikov E., Fedirko V., Daniel C.R., Rutherford R.E., Shaukat A., Bostick R.M. A randomized clinical trial of the effects of supplemental calcium and vitamin D3 on markers of their metabolism in normal mucosa of colorectal adenoma patients. Cancer Res. 2011, 71:413-423.
69. Whitfield J. Calcium switches, cell cycles, differentiation and, death 1991, CRC Press.
70. Whitfield J.F. The calcium-sensing receptor-a driver of colon cell differentiation. Curr. Pharm. Biotechnol. 2009, 10:311-316.
71. Whitfield J.F. Calcium, calcium-sensing receptor and colon cancer. Cancer Lett. 2009, 275:9-16.
72. Gama L., Baxendale-Cox L.M., Breitwieser G.E. Ca2+-sensing receptors in intestinal epithelium. Am. J. Physiol. 1997, 273:C1168-C1175.
73. Sheinin Y., Kallay E., Wrba F., Kriwanek S., Peterlik M., Cross H.S. Immunocytochemical localization of the extracellular calcium-sensing receptor in normal and malignant human large intestinal mucosa. J. Histochem. Cytochem. 2000, 48:595-602.
74. Cheng S.X. Calcium-sensing receptor inhibits secretagogue-induced electrolyte secretion by intestine via the enteric nervous system. Am. J. Physiol. Gastrointest. Liver Physiol. 2012, 303:G60-G70.
75. Chakrabarty S., Wang H., Canaff L., Hendy G.N., Appelman H., Varani J. Calcium sensing receptor in human colon carcinoma: interaction with Ca(2+) and 1,25-dihydroxyvitamin D(3). Cancer Res. 2005, 65:493-498.
76. Chakrabarty S., Radjendirane V., Appelman H., Varani J. Extracellular calcium and calcium sensing receptor function in human colon carcinomas: promotion of E-cadherin expression and suppression of beta-catenin/TCF activation. Cancer Res. 2003, 63:67-71.
77. Ahearn T.U., McCullough M.L., Flanders W.D., Long Q., Sidelnikov E., Fedirko V., Daniel C.R., Rutherford R.E., Shaukat A., Bostick R.M. A randomized clinical trial of the effects of supplemental calcium and vitamin D3 on markers of their metabolism in normal mucosa of colorectal adenoma patients. Cancer Res. 2011, 71:413-423.
78. Brenner B.M., Russell N., Albrecht S., Davies R.J. The effect of dietary vitamin D3 on the intracellular calcium gradient in mammalian colonic crypts. Cancer Lett. 1998, 127:43-53.
79. Hizaki K., Yamamoto H., Taniguchi H., Adachi Y., Nakazawa M., Tanuma T., Kato N., Sukawa Y., Sanchez J.V., Suzuki H., Sasaki S., Imai K., Shinomura Y. Epigenetic inactivation of calcium-sensing receptor in colorectal carcinogenesis. Mod. Pathol. 2011, 24:876-884.
80. Jones P.A., Baylin S.B. The fundamental role of epigenetic events in cancer. Nat. Rev. Genet. 2002, 3:415-428.
81. Kulis M., Esteller M. DNA methylation and cancer. Adv. Genet. 2010, 70:27-56.
82. Wang Y., Leung F.C. An evaluation of new criteria for CpG islands in the human genome as gene markers. Bioinformatics 2004, 20:1170-1177.
83. Chikatsu N., Fukumoto S., Takeuchi Y., Suzawa M., Obara T., Matsumoto T., Fujita T. Cloning and characterization of two promoters for the human calcium-sensing receptor (CaSR) and changes of CaSR expression in parathyroid adenomas. J. Biol. Chem. 2000, 275:7553-7557.
84. Canaff L., Hendy G.N. Human calcium-sensing receptor gene. Vitamin D response elements in promoters P1 and P2 confer transcriptional responsiveness to 1,25-dihydroxyvitamin D. J. Biol. Chem. 2002, 277:30337-30350.
85. Kallay E., Bonner E., Wrba F., Thakker R.V., Peterlik M., Cross H.S. Molecular and functional characterization of the extracellular calcium-sensing receptor in human colon cancer cells. Oncol. Res. 2003, 13:551-559.
86. Canaff L., Hendy G.N. Calcium-sensing receptor gene transcription is up-regulated by the proinflammatory cytokine, interleukin-1beta. Role of the NF-kappaB PATHWAY and kappaB elements. J. Biol. Chem. 2005, 280:14177-14188.
87. Canaff L., Zhou X., Hendy G.N. The proinflammatory cytokine, interleukin-6, up-regulates calcium-sensing receptor gene transcription via Stat1/3 and Sp1/3. J. Biol. Chem. 2008, 283:13586-13600.
88. Horváth H.C., Lakatos P., Kósa J.P., Bácsi K., Borka K., Bises G., Nittke T., Hershberger P.A., Speer G., Kállay E. The candidate oncogene CYP24A1: a potential biomarker for colorectal tumorigenesis. J. Histochem. Cytochem. 2010, 58:277-285.
89. Bhagavathula N., Kelley E.A., Reddy M., Nerusu K.C., Leonard C., Fay K., Chakrabarty S., Varani J. Upregulation of calcium-sensing receptor and mitogen-activated protein kinase signalling in the regulation of growth and differentiation in colon carcinoma. Br. J. Cancer 2005, 93:1364-1371.
90. Bhagavathula N., Hanosh A.W., Nerusu K.C., Appelman H., Chakrabarty S., Varani J. Regulation of E-cadherin and beta-catenin by Ca2+ in colon carcinoma is dependent on calcium-sensing receptor expression and function. Int. J. Cancer 2007, 121:1455-1462.
91. Rey O., Young S.H., Jacamo R., Moyer M.P., Rozengurt E. Extracellular calcium sensing receptor stimulation in human colonic epithelial cells induces intracellular calcium oscillations and proliferation inhibition. J. Cell. Physiol. 2010, 225:73-83.
92. Moon R.T., Kohn A.D., De Ferrari G.V., Kaykas A. WNT and beta-catenin signalling: diseases and therapies. Nat. Rev. Genet. 2004, 5:691-701.
93. Clevers H., Nusse R. Wnt/beta-catenin signaling and disease. Cell 2012, 149:1192-1205.
94. Burgess A.W., Faux M.C., Layton M.J., Ramsay R.G. Wnt signaling and colon tumorigenesis-a view from the periphery. Exp. Cell Res. 2011, 317:2748-2758.
95. Kuhnert F., Davis C.R., Wang H.T., Chu P., Lee M., Yuan J., Nusse R., Kuo C.J. Essential requirement for Wnt signaling in proliferation of adult small intestine and colon revealed by adenoviral expression of Dickkopf-1. Proc. Natl. Acad. Sci. U. S. A. 2004, 101:266-271.
96. Clarke A.R. Wnt signalling in the mouse intestine. Oncogene 2006, 25:7512-7521.
97. Pacheco I.I., Macleod R.J. CaSR stimulates secretion of Wnt5a from colonic myofibroblasts to stimulate CDX2 and sucrase-isomaltase using Ror2 on intestinal epithelia. Am. J. Physiol. Gastrointest. Liver Physiol. 2008, 295:G748-G759.
98. Najdi R., Holcombe R.F., Waterman M.L. Wnt signaling and colon carcinogenesis: beyond APC. J. Carcinog. 2011, 10:5.
99. MacLeod R.J., Hayes M., Pacheco I. Wnt5a secretion stimulated by the extracellular calcium-sensing receptor inhibits defective Wnt signaling in colon cancer cells. Am. J. Physiol. Gastrointest. Liver Physiol. 2007, 293:G403-G411.
100. Kelly J.C., Lungchukiet P., Macleod R.J. Extracellular calcium-sensing receptor inhibition of intestinal epithelialTNF signaling requires CaSR-mediated Wnt5a/Ror2 interaction. Front. Physiol. 2011, 2:17.
101. Moskaluk C.A., Zhang H., Powell S.M., Cerilli L.A., Hampton G.M., Frierson H.F. Cdx2 protein expression in normal and malignant human tissues: an immunohistochemical survey using tissue microarrays. Mod. Pathol. 2003, 16:913-919.
102. Mallo G.V., Soubeyran P., Lissitzky J.C., Andre F., Farnarier C., Marvaldi J., Dagorn J.C., Iovanna J.L. Expression of the Cdx1 and Cdx2 homeotic genes leads to reduced malignancy in colon cancer-derived cells. J. Biol. Chem. 1998, 273:14030-14036.
103. Gross I., Duluc I., Benameur T., Calon A., Martin E., Brabletz T., Kedinger M., Domon-Dell C., Freund J.N. The intestine-specific homeobox gene Cdx2 decreases mobility and antagonizes dissemination of colon cancer cells. Oncogene 2008, 27:107-115.
104. Buset M., Lipkin M., Winawer S., Swaroop S., Friedman E. Inhibition of human colonic epithelial cell proliferation in vivo and in vitro by calcium. Cancer Res. 1986, 46:5426-5430.
105. Rogers A.C., Hanly A.M., Collins D., Baird A.W., Winter D.C. Review article: loss of the calcium-sensing receptor in colonic epithelium is a key event in the pathogenesis of colon cancer. Clin. Colorectal Cancer 2012, 11:24-30.
106. SEER Cancer Statistics Review, 1975-2009 (Vintage 2009 Populations) 2012, National Cancer Institute, (http://seer.cancer.gov/csr/1975_2009_pops1909/index.html accessed July 19, 2012). N. Howlader, A.M. Noone, M. Krapcho, N. Neyman, R. Aminou, S.F. Altekruse, C.L. Kosary, J. Ruhl, Z. Tatalovich, H. Cho, A. Mariotto, M.P. Eisner, D.R. Lewis, H.S. Chen, E.J. Feuer, K.A. Cronin (Eds.).
107. Cui Y., Rohan T.E. Vitamin D, calcium, and breast cancer risk: a review. Cancer Epidemiol. Biomarkers Prev. 2006, 15:1427-1437.
108. Huncharek M., Muscat J., Kupelnick B. Colorectal cancer risk and dietary intake of calcium, vitamin D, and dairy products: a meta-analysis of 26,335 cases from 60 observational studies. Nutr. Cancer 2009, 61:47-69.
109. Chlebowski R.T., Johnson K.C., Kooperberg C., Pettinger M., Wactawski-Wende J., Rohan T., Rossouw J., Lane D., O'Sullivan M.J., Yasmeen S., Hiatt R.A., Shikany J.M., Vitolins M., Khandekar J., Hubbell F.A. Calcium plus vitamin D supplementation and the risk of breast cancer. J. Natl. Cancer Inst. 2008, 100:1581-1591.
110. Larsson S.C., Bergkvist L., Wolk A. Long-term dietary calcium intake and breast cancer risk in a prospective cohort of women. Am. J. Clin. Nutr. 2009, 89:277-282.
111. Moorman P.G., Terry P.D. Consumption of dairy products and the risk of breast cancer: a review of the literature. Am. J. Clin. Nutr. 2004, 80:5-14.
112. Bissonauth V., Shatenstein B., Ghadirian P. Nutrition and breast cancer among sporadic cases and gene mutation carriers: an overview. Cancer Detect. Prev. 2008, 32:52-64.
113. Parodi P.W. Dairy product consumption and the risk of breast cancer. J. Am. Coll. Nutr. 2005, 24:556S-568S.
114. Al Sarakbi W., Salhab M., Mokbel K. Dairy products and breast cancer risk: a review of the literature. Int. J. Fertil. Womens Med. 2005, 50:244-249.
115. Abbas S., Linseisen J., Chang-Claude J. Dietary vitamin D and calcium intake and premenopausal breast cancer risk in a German case-control study. Nutr. Cancer 2007, 59:54-61.
116. Baron J.A., Beach M., Wallace K., Grau M.V., Sandler R.S., Mandel J.S., Heber D., Greenberg E.R. Risk of prostate cancer in a randomized clinical trial of calcium supplementation. Cancer Epidemiol. Biomarkers Prev. 2005, 14:586-589.
117. Cheng I., Klingensmith M.E., Chattopadhyay N., Kifor O., Butters R.R., Soybel D.I., Brown E.M. Identification and localization of the extracellular calcium-sensing receptor in human breast. J. Clin. Endocrinol. Metab. 1998, 83:703-707.
118. VanHouten J.N., Neville M.C., Wysolmerski J.J. The calcium-sensing receptor regulates plasma membrane calcium adenosine triphosphatase isoform 2 activity in mammary epithelial cells: a mechanism for calcium-regulated calcium transport into milk. Endocrinology 2007, 148:5943-5954.
119. Mihai R., Stevens J., McKinney C., Ibrahim N.B. Expression of the calcium receptor in human breast cancer-a potential new marker predicting the risk of bone metastases. Eur. J. Surg. Oncol. 2006, 32:511-515.
120. Saidak Z., Boudot C., Abdoune R., Petit L., Brazier M., Mentaverri R., Kamel S. Extracellular calcium promotes the migration of breast cancer cells through the activation of the calcium sensing receptor. Exp. Cell Res. 2009, 315:2072-2080.
121. Sanders J.L., Chattopadhyay N., Kifor O., Yamaguchi T., Brown E.M. Ca(2+)-sensing receptor expression and PTHrP secretion in PC-3 human prostate cancer cells. Am. J. Physiol. Endocrinol. Metab. 2001, 281:E1267-E1274.
122. Liao J., Schneider A., Datta N.S., McCauley L.K. Extracellular calcium as a candidate mediator of prostate cancer skeletal metastasis. Cancer Res. 2006, 66:9065-9073.
123. Biswas D.K., Shi Q., Baily S., Strickland I., Ghosh S., Pardee A.B., Iglehart J.D. NF-kappa B activation in human breast cancer specimens and its role in cell proliferation and apoptosis. Proc. Natl. Acad. Sci. U. S. A. 2004, 101:10137-10142.
124. Connelly L., Barham W., Onishko H.M., Sherrill T., Chodosh L.A., Blackwell T.S., Yull F.E. Inhibition of NF-kappa B activity in mammary epithelium increases tumor latency and decreases tumor burden. Oncogene 2011, 30:1402-1412.
125. Höbaus J., Thiem U., Hummel D.M., Kallay E. Role of calcium, Vitamin D, and the extrarenal vitamin D hydroxylases during carcinogenesis. Anticancer Agents Med. Chem. 2012, 13:20-35.
126. El Hiani Y., Lehen'kyi V., Ouadid-Ahidouch H., Ahidouch A. Activation of the calcium-sensing receptor by high calcium induced breast cancer cell proliferation and TRPC1 cation channel over-expression potentially through EGFR pathways. Arch. Biochem. Biophys. 2009, 486:58-63.
127. Vivacqua A., Lappano R., De Marco P., Sisci D., Aquila S., De Amicis F., Fuqua S.A., Ando S., Maggiolini M. G protein-coupled receptor 30 expression is up-regulated by EGF and TGF alpha in estrogen receptor alpha-positive cancer cells. Mol. Endocrinol. 2009, 23:1815-1826.
128. Breitwieser G.E. Minireview: the intimate link between calcium sensing receptor trafficking and signaling: implications for disorders of calcium homeostasis. Mol. Endocrinol. 2012, 26:1482-1495.
129. El Hiani Y., Ahidouch A., Lehen'kyi V., Hague F., Gouilleux F., Mentaverri R., Kamel S., Lassoued K., Brule G., Ouadid-Ahidouch H. Extracellular signal-regulated kinases 1 and 2 and TRPC1 channels are required for calcium-sensing receptor-stimulated MCF-7 breast cancer cell proliferation. Cell. Physiol. Biochem. 2009, 23:335-346.
130. Liu G., Hu X., Chakrabarty S. Calcium sensing receptor down-regulates malignant cell behavior and promotes chemosensitivity in human breast cancer cells. Cell Calcium 2009, 45:216-225.
131. Roodman G.D. Mechanisms of bone metastasis. N. Engl. J. Med. 2004, 350:1655-1664.
132. Thomas R.J., Guise T.A., Yin J.J., Elliott J., Horwood N.J., Martin T.J., Gillespie M.T. Breast cancer cells interact with osteoblasts to support osteoclast formation. Endocrinology 1999, 140:4451-4458.
133. Brown J.M., Corey E., Lee Z.D., True L.D., Yun T.J., Tondravi M., Vessella R.L. Osteoprotegerin and rank ligand expression in prostate cancer. Urology 2001, 57:611-616.
134. Powell G.J., Southby J., Danks J.A., Stillwell R.G., Hayman J.A., Henderson M.A., Bennett R.C., Martin T.J. Localization of parathyroid hormone-related protein in breast cancer metastases: increased incidence in bone compared with other sites. Cancer Res. 1991, 51:3059-3061.
135. Stewart A.F. Clinical practice. Hypercalcemia associated with cancer. N. Engl. J. Med. 2005, 352:373-379.
136. VanHouten J.N. Calcium sensing by the mammary gland. J. Mammary Gland Biol. Neoplasia 2005, 10:129-139.
137. Sanders J.L., Chattopadhyay N., Kifor O., Yamaguchi T., Butters R.R., Brown E.M. Extracellular calcium-sensing receptor expression and its potential role in regulating parathyroid hormone-related peptide secretion in human breast cancer cell lines. Endocrinology 2000, 141:4357-4364.
138. Yano S., Macleod R.J., Chattopadhyay N., Tfelt-Hansen J., Kifor O., Butters R.R., Brown E.M. Calcium-sensing receptor activation stimulates parathyroid hormone-related protein secretion in prostate cancer cells: role of epidermal growth factor receptor transactivation. Bone 2004, 35:664-672.
139. Jones D.H., Nakashima T., Sanchez O.H., Kozieradzki I., Komarova S.V., Sarosi I., Morony S., Rubin E., Sarao R., Hojilla C.V., Komnenovic V., Kong Y.Y., Schreiber M., Dixon S.J., Sims S.M., Khokha R., Wada T., Penninger J.M. Regulation of cancer cell migration and bone metastasis by RANKL. Nature 2006, 440:692-696.
140. Smith M.C., Luker K.E., Garbow J.R., Prior J.L., Jackson E., Piwnica-Worms D., Luker G.D. CXCR4 regulates growth of both primary and metastatic breast cancer. Cancer Res. 2004, 64:8604-8612.
141. Sun Y.X., Schneider A., Jung Y., Wang J., Dai J., Cook K., Osman N.I., Koh-Paige A.J., Shim H., Pienta K.J., Keller E.T., McCauley L.K., Taichman R.S. Skeletal localization and neutralization of the SDF-1(CXCL12)/CXCR4 axis blocks prostate cancer metastasis and growth in osseous sites in vivo. J. Bone Miner. Res. 2005, 20:318-329.
142. Kang Y., Siegel P.M., Shu W., Drobnjak M., Kakonen S.M., Cordon-Cardo C., Guise T.A., Massague J. A multigenic program mediating breast cancer metastasis to bone. Cancer Cell 2003, 3:537-549.
143. Sethi N., Kang Y. Dysregulation of developmental pathways in bone metastasis. Bone 2011, 48:16-22.
144. Leach K., Wen A., Davey A.E., Sexton P.M., Conigrave A.D., Christopoulos A. Identification of molecular phenotypes and biased signaling induced by naturally occurring mutations of the human calcium-sensing receptor. Endocrinology 2012, 153:4304-4316.
145. Davey A.E., Leach K., Valant C., Conigrave A.D., Sexton P.M., Christopoulos A. Positive and negative allosteric modulators promote biased signaling at the calcium-sensing receptor. Endocrinology 2012, 153:1232-1241.
146. Jensen A.A., Brauner-Osborne H. Allosteric modulation of the calcium-sensing receptor. Curr. Neuropharmacol. 2007, 5:180-186.
147. Kholodenko B.N., Hancock J.F., Kolch W. Signalling ballet in space and time. Nat. Rev. Mol. Cell Biol. 2010, 11:414-426.
148. Grecco H.E., Schmick M., Bastiaens P.I. Signaling from the living plasma membrane. Cell 2011, 144:897-909.
149. Adjobo-Hermans M.J., Goedhart J., van W.L., Nijmeijer S., Manders E.M., Offermanns S., Gadella T.W. Real-time visualization of heterotrimeric G protein Gq activation in living cells. BMC Biol. 2011, 9:32.
150. Janetopoulos C., Jin T., Devreotes P. Receptor-mediated activation of heterotrimeric G-proteins in living cells. Science 2001, 291:2408-2411.
151. Grimsrud P.A., Swaney D.L., Wenger C.D., Beauchene N.A., Coon J.J. Phosphoproteomics for the masses. ACS Chem. Biol. 2010, 5:105-119.
152. Rubbi L., Titz B., Brown L., Galvan E., Komisopoulou E., Chen S.S., Low T., Tahmasian M., Skaggs B., Muschen M., Pellegrini M., Graeber T.G. Global phosphoproteomics reveals crosstalk between Bcr-Abl and negative feedback mechanisms controlling Src signaling. Sci. Signal. 2011, 4:ra18.
153. Gujral T.S., Karp R.L., Finski A., Chan M., Schwartz P.E., Macbeath G., Sorger P. Profiling phospho-signaling networks in breast cancer using reverse-phase protein arrays. Oncogene 2012, [Sep. 3, Electronic publication ahead of print].
154. Kholodenko B., Yaffe M.B., Kolch W. Computational approaches for analyzing information flow in biological networks. Sci. Signal. 2012, 5:re1.
155. Changeux J.P., Edelstein S.J. Allosteric mechanisms of signal transduction. Science 2005, 308:1424-1428.
156. De Luca F., Ray K., Mancilla E.E., Fan G.F., Winer K.K., Gore P., Spiegel A.M., Baron J. Sporadic hypoparathyroidism caused by de novo gain-of-function mutations of the Ca(2+)-sensing receptor. J. Clin. Endocrinol. Metab. 1997, 82:2710-2715.
157. Pollak M.R., Brown E.M., Estep H.L., McLaine P.N., Kifor O., Park J., Hebert S.C., Seidman C.E., Seidman J.G. Autosomal dominant hypocalcaemia caused by a Ca(2+)-sensing receptor gene mutation. Nat. Genet. 1994, 8:303-307.
158. Mun H.C., Culverston E.L., Franks A.H., Collyer C.A., Clifton-Bligh R.J., Conigrave A.D. A double mutation in the extracellular Ca2+-sensing receptor's venus flytrap domain that selectively disables L-amino acid sensing. J. Biol. Chem. 2005, 280:29067-29072.
159. Terranegra A., Ferraretto A., Dogliotti E., Scarpellini M., Corbetta S., Barbieri A.M., Spada A., Arcidiacono T., Rainone F., Aloia A., Cusi D., Vezzoli G., Soldati L. Calcimimetic R-568 effects on activity of R990G polymorphism of calcium-sensing receptor. J. Mol. Endocrinol. 2010, 45:245-256.
160. Ray K., Hauschild B.C., Steinbach P.J., Goldsmith P.K., Hauache O., Spiegel A.M. Identification of the cysteine residues in the amino-terminal extracellular domain of the human Ca(2+) receptor critical for dimerization. Implications for function of monomeric Ca(2+) receptor. J. Biol. Chem. 1999, 274:27642-27650.
161. May L.T., Leach K., Sexton P.M., Christopoulos A. Allosteric modulation of G protein-coupled receptors. Annu. Rev. Pharmacol. Toxicol. 2007, 47:1-51.
162. Changeux J.P., Edelstein S. Conformational selection or induced fit? 50years of debate resolved. F1000 Biol. Rep. 2011, 3:19.
163. Shenker A. G protein-coupled receptor structure and function: the impact of disease-causing mutations. Baillieres Clin. Endocrinol. Metab. 1995, 9:427-451.
164. Kenakin T. Functional selectivity and biased receptor signaling. J. Pharmacol. Exp. Ther. 2011, 336:296-302.
165. Thomsen A.R., Hvidtfeldt M., Brauner-Osborne H. Biased agonism of the calcium-sensing receptor. Cell Calcium 2012, 51:107-116.
166. Thomsen A.R., Worm J., Jacobsen S.E., Stahlhut M., Latta M., Brauner-Osborne H. Strontium is a biased agonist of the calcium-sensing receptor in rat medullary thyroid carcinoma 6-23 cells. J. Pharmacol. Exp. Ther. 2012, 343:638-649.
167. Mulder D.J., Pacheco I., Hurlbut D.J., Mak N., Furuta G.T., MacLeod R.J., Justinich C.J. FGF9-induced proliferative response to eosinophilic inflammation in oesophagitis. Gut 2009, 58:166-173.
168. Liu G., Hu X., Varani J., Chakrabarty S. Calcium and calcium sensing receptor modulates the expression of thymidylate synthase, NAD(P)H:quinone oxidoreductase 1 and survivin in human colon carcinoma cells: promotion of cytotoxic response to mitomycin C and fluorouracil. Mol. Carcinog. 2009, 48:202-211.
169. Kawata T., Imanishi Y., Kobayashi K., Kenko T., Wada M., Ishimura E., Miki T., Nagano N., Inaba M., Arnold A., Nishizawa Y. Relationship between parathyroid calcium-sensing receptor expression and potency of the calcimimetic, cinacalcet, in suppressing parathyroid hormone secretion in an in vivo murine model of primary hyperparathyroidism. Eur. J. Endocrinol. 2005, 153:587-594.
170. Liu G., Hu X., Chakrabarty S. Vitamin D mediates its action in human colon carcinoma cells in a calcium-sensing receptor-dependent manner: downregulates malignant cell behavior and the expression of thymidylate synthase and survivin and promotes cellular sensitivity to 5-FU. Int. J. Cancer 2010, 126:631-639.
171. Liu G., Hu X., Varani J., Chakrabarty S. Calcium and calcium sensing receptor modulates the expression of thymidylate synthase, NAD(P)H:quinone oxidoreductase 1 and survivin in human colon carcinoma cells: promotion of cytotoxic response to mitomycin C and fluorouracil. Mol. Carcinog. 2009, 48:202-211.
172. Promkan M., Liu G., Patmasiriwat P., Chakrabarty S. BRCA1 suppresses the expression of survivin and promotes sensitivity to paclitaxel through the calcium sensing receptor (CaSR) in human breast cancer cells. Cell Calcium 2011, 49:79-88.
173. Fox J., Lowe S.H., Conklin R.L., Petty B.A., Nemeth E.F. Calcimimetic compound NPS R-568 stimulates calcitonin secretion but selectively targets parathyroid gland Ca(2+) receptor in rats. J. Pharmacol. Exp. Ther. 1999, 290:480-486.
174. Cheng S.X., Geibel J.P., Hebert S.C. Extracellular polyamines regulate fluid secretion in rat colonic crypts via the extracellular calcium-sensing receptor. Gastroenterology 2004, 126:148-158.
175. Liou A.P., Sei Y., Zhao X., Feng J., Lu X., Thomas C., Pechhold S., Raybould H.E., Wank S.A. The extracellular calcium-sensing receptor is required for cholecystokinin secretion in response to L-phenylalanine in acutely isolated intestinal I cells. Am. J. Physiol. Gastrointest. Liver Physiol. 2011, 300:G538-G546.
176. Wang Y., Chandra R., Samsa L.A., Gooch B., Fee B.E., Cook J.M., Vigna S.R., Grant A.O., Liddle R.A. Amino acids stimulate cholecystokinin release through the Ca2+-sensing receptor. Am. J. Physiol. Gastrointest. Liver Physiol. 2011, 300:G528-G537.
177. Ohsu T., Amino Y., Nagasaki H., Yamanaka T., Takeshita S., Hatanaka T., Maruyama Y., Miyamura N., Eto Y. Involvement of the calcium-sensing receptor in human taste perception. J. Biol. Chem. 2010, 285:1016-1022.
178. Cheung R., Kelly J., Macleod R.J. Regulation of villin by wnt5a/ror2 signaling in human intestinal cells. Front. Physiol. 2011, 2:58.
179. MacLeod R.J., Hayes M., Pacheco I. Wnt5a secretion stimulated by the extracellular calcium-sensing receptor inhibits defective Wnt signaling in colon cancer cells. Am. J. Physiol. Gastrointest. Liver Physiol. 2007, 293:G403-G411.
180. Pacheco R.J. Macleod, CaSR stimulates secretion of Wnt5a from colonic myofibroblasts to stimulate CDX2 and sucrase-isomaltase using Ror2 on intestinal epithelia. Am. J. Physiol. Gastrointest. Liver Physiol. 2008, 295:G748-G759.
181. Chang W., Shoback D. Extracellular Ca2+-sensing receptors-an overview. Cell Calcium 2004, 35:183-196.
182. Chakravarti B., Dwivedi S.K., Mithal A., Chattopadhyay N. Calcium-sensing receptor in cancer: good cop or bad cop?. Endocrine 2009, 35:271-284.