Human VRK2 (vaccinia-related kinase 2) modulates tumor cell invasion by hyperactivation of NFAT1 and expression of cyclooxygenase-2

Journal of Biological Chemistry

Volumn 287, Issue 51, 2012, Pages 42739-42750

  Vázquez Cedeira, Marta ^a,b   Lazo, Pedro A ^a  

^a CSIC   (Spain)

^b HOSPITAL UNIVERSITARIO DE SALAMANCA   (Spain)

Author keywords

[No Author keywords available]

Indexed keywords

CALCINEURIN; CANCER CELLS; CELL INVASION; CYCLOOXYGENASE 2; DOWN-REGULATION; GENE PROMOTER; HYPERACTIVATION; IONOMYCIN; N-TERMINAL TRANSACTIVATION; NUCLEAR FACTOR OF ACTIVATED T-CELLS; PHORBOL 12 MYRISTATE 13 ACETATES; PROTEIN LEVEL; RNA INTERFERENCE; SIGNALING PATHWAYS; TUMOR CELL INVASION; TUMOR CELLS;

CYTOLOGY; ENZYME INHIBITION; GENES; PHOSPHORYLATION; PROTEINS; RNA; TRANSCRIPTION; TUMORS; VOLATILE FATTY ACIDS;

CELLS;

CALCINEURIN; CELL PROTEIN; CYCLOOXYGENASE 2; IONOMYCIN; PHORBOL 13 ACETATE 12 MYRISTATE; SERINE; TRANSCRIPTION FACTOR NFAT; TRANSCRIPTION FACTOR NFAT1; UNCLASSIFIED DRUG; VACCINIA RELATED KINASE 2;

AMINO TERMINAL SEQUENCE; ARTICLE; BINDING SITE; BREAST CANCER; CANCER CELL CULTURE; CELL INVASION; CONTROLLED STUDY; CYCLOOXYGENASE 2 GENE; DOWN REGULATION; GENE EXPRESSION REGULATION; HUMAN; HUMAN CELL; PRIORITY JOURNAL; PROMOTER REGION; PROTEIN DOMAIN; PROTEIN EXPRESSION; PROTEIN FUNCTION; PROTEIN PHOSPHORYLATION; PROTEIN PROTEIN INTERACTION; RNA INTERFERENCE; SIGNAL TRANSDUCTION; TRANSCRIPTION INITIATION; UPREGULATION;

ANIMALS; BINDING SITES; CELL LINE, TUMOR; CYCLOOXYGENASE 2; GENE EXPRESSION REGULATION, NEOPLASTIC; GENE SILENCING; HUMANS; INTRACELLULAR SIGNALING PEPTIDES AND PROTEINS; IONOMYCIN; ISOENZYMES; MICE; MODELS, BIOLOGICAL; MUSCLE PROTEINS; NEOPLASM INVASIVENESS; NEOPLASMS; NFATC TRANSCRIPTION FACTORS; PHOSPHORYLATION; PHOSPHOSERINE; PROTEIN BINDING; PROTEIN STRUCTURE, TERTIARY; PROTEIN-SERINE-THREONINE KINASES; RESPONSE ELEMENTS; RNA, MESSENGER; TETRADECANOYLPHORBOL ACETATE; TRANSCRIPTION, GENETIC;

EID: 84871128788     PISSN: 00219258     EISSN: 1083351X     Source Type: Journal    
DOI: 10.1074/jbc.M112.404285     Document Type: Article

References (68)

1. Kim, T. H., Kim, H. I., Soung, Y. H., Shaw, L. A., and Chung, J. (2009) Integrin (α6β4) signals through Src to increase expression of S100A4, a metastasis-promoting factor. Implications for cancer cell invasion. Mol. Cancer Res. 7, 1605-1612
2. Ryeom, S., Baek, K. H., Rioth, M. J., Lynch, R. C., Zaslavsky, A., Birsner, A., Yoon, S. S., and McKeon, F. (2008) Targeted deletion of the calcineurin inhibitor DSCR1 suppresses tumor growth. Cancer Cell 13, 420-431 (Pubitemid 351609439)
3. Buchholz, M., Schatz, A., Wagner, M., Michl, P., Linhart, T., Adler, G., Gress, T. M., and Ellenrieder, V. (2006) Overexpression of c-myc in pancreatic cancer caused by ectopic activation of NFATc1 and the Ca2+/calcineurin signaling pathway, EMBO J. 25, 3714-3724 (Pubitemid 44264881)
4. Jiang, X., Austin, P. F., Niederhoff, R. A., Manson, S. R., Riehm, J. J., Cook, B. L., Pengue, G., Chitaley, K., Nakayama, K., Nakayama, K. I., and Weintraub, S. J. (2009) Mechanoregulation of proliferation. Mol. Cell. Biol. 29, 5104-5114
5. Mancini, M., and Toker, A. (2009) NFAT proteins. Emerging roles in cancer progression. Nat. Rev. Cancer 9, 810-820
6. Manning, G., Whyte, D. B., Martinez, R., Hunter, T., and Sudarsanam, S. (2002) The protein kinase complement of the human genome. Science 298, 1912-1934 (Pubitemid 35425239)
7. Nezu, J., Oku, A., Jones, M. H., and Shimane, M. (1997) Identification of two novel human putative serine/threonine kinases, VRK1 and VRK2, with structural similarity to vaccinia virus B1R kinase. Genomics 45, 327-331 (Pubitemid 27467623)
8. Lopez-Borges, S., and Lazo, P. A. (2000) The human vaccinia-related kinase 1 (VRK1) phosphorylates threonine-18 within the mdm-2 binding site of the p53 tumour suppressor protein. Oncogene 19, 3656-3664 (Pubitemid 30608487)
9. Nichols, R. J., and Traktman, P. (2004) Characterization of three paralogous members of the Mammalian vaccinia related kinase family. J. Biol. Chem. 279, 7934-7946 (Pubitemid 38294681)
10. Klerkx, E. P., Lazo, P. A., and Askjaer, P. (2009) Emerging biological functions of the vaccinia-related kinase (VRK) family. Histol. Histopathol. 24, 749-759
11. Vega, F. M., Gonzalo, P., Gaspar, M. L., and Lazo, P. A. (2003) Expression of the VRK (vaccinia-related kinase) gene family of p53 regulators in murine hematopoietic development. FEBS Lett. 544, 176-180 (Pubitemid 36628057)
12. Santos, C. R., Rodríguez-Pinilla, M., Vega, F. M., Rodríguez-Peralto, J. L.,Blanco, S., Sevilla, A., Valbuena, A., Hernández, T., van Wijnen, A. J., Li, F., de Alava, E., Sánchez-Céspedes, M., and Lazo, P. A. (2006) VRK1 signaling pathway in the context of the proliferation phenotype in head and neck squamous cell carcinoma. Mol. Cancer Res. 4, 177-185
13. Valbuena, A., Sanz-García, M., López-Sánchez, I., Vega, F. M., and Lazo,P. A. (2011) Roles of VRK1 as a new player in the control of biological processes required for cell division. Cell. Signal. 23, 1267-1272
14. Valbuena, A., López-Sánchez, I., and Lazo, P. A. (2008) Human VRK1 is an early response gene and its loss causes a block in cell cycle progression. PLoS ONE 3, e1642
15. Barcia, R., López-Borges, S., Vega, F. M., and Lazo, P. A. (2002) Kinetic properties of p53 phosphorylation by the human vaccinia-related kinase 1. Arch. Biochem. Biophys. 399, 1-5 (Pubitemid 34848304)
16. Vega, F. M., Sevilla, A., and Lazo, P. A. (2004) p53 Stabilization and accumulation induced by human vaccinia-related kinase 1. Mol. Cell. Biol. 24, 10366-10380 (Pubitemid 39507873)
17. Valbuena, A., Vega, F. M., Blanco, S., and Lazo, P. A. (2006) p53 downregulates its activating vaccinia-related kinase 1, forming a new autoregulatory loop. Mol. Cell. Biol. 26, 4782-4793 (Pubitemid 43955797)
18. Valbuena, A., Blanco, S., Vega, F. M., and Lazo, P. A. (2008) The C/H3 domain of p300 is required to protect VRK1 and VRK2 from their downregulation induced by p53. PLoS ONE 3, e2649
19. Valbuena, A., Castro-Obregón, S., and Lazo, P. A. (2011) Downregulation of VRK1 by p53 in response to DNA damage is mediated by the autophagic pathway. PLoS ONE 6, e17320
20. Sevilla, A., Santos, C. R., Barcia, R., Vega, F. M., and Lazo, P. A. (2004) c-Jun phosphorylation by the human vaccinia-related kinase 1 (VRK1) and its cooperation with the N-terminal kinase of c-Jun (JNK). Oncogene 23, 8950-8958 (Pubitemid 39657785)
21. Sevilla, A., Santos, C. R., Vega, F. M., and Lazo, P. A. (2004) Human vaccinia-related kinase 1 (VRK1) activates the ATF2 transcriptional activity by novel phosphorylation on Thr-73 and Ser-62 and cooperates with JNK. J. Biol. Chem. 279, 27458-27465 (Pubitemid 38812585)
22. Kang, T. H., Park, D. Y., Kim, W., and Kim, K. T. (2008) VRK1 phosphorylates CREB and mediates CCND1 expression. J. Cell Sci. 121, 3035-3041
23. Fernández, I. F., Blanco, S., Lozano, J., and Lazo, P. A. (2010) VRK2 inhibits mitogen-activated protein kinase signaling and inversely correlates with ErbB2 in human breast cancer. Mol. Cell. Biol. 30, 4687-4697
24. Blanco, S., Klimcakova, L., Vega, F. M., and Lazo, P. A. (2006) The subcellular localization of vaccinia-related kinase-2 (VRK2) isoforms determines their different effect on p53 stability in tumour cell lines. FEBS J. 273, 2487-2504 (Pubitemid 43736661)
25. Blanco, S., Santos, C., and Lazo, P. A. (2007) Vaccinia-related kinase 2 modulates the stress response to hypoxia mediated by TAK1. Mol. Cell. Biol. 27, 7273-7283 (Pubitemid 47549760)
26. Blanco, S., Sanz-García, M., Santos, C. R., and Lazo, P. A. (2008) Modulationof interleukin-1 transcriptional response by the interaction between VRK2 and the JIP1 scaffold protein. PLoS ONE 3, e1660
27. Fernández, I. F., Pérez-Rivas, L. G., Blanco, S., Castillo-Dominguez, A. A., Lozano, J., and Lazo, P. A. (2012) VRK2 anchors KSR1-MEK1 to endoplasmic reticulum forming a macromolecular complex that compartmentalizes MAPK signaling. Cell Mol. Life Sci. 69, 3881-3893
28. Rao, A., Luo, C., and Hogan, P. G. (1997) Transcription factors of the NFAT family. Regulation and function. Annu. Rev. Immunol. 15, 707-747 (Pubitemid 27169297)
29. Serfling, E., Berberich-Siebelt, F., Chuvpilo, S., Jankevics, E., Klein-Hessling, S., Twardzik, T., and Avots, A. (2000) The role of NF-AT transcription factors in T cell activation and differentiation, Biochim. Biophys. Acta 1498, 1-18
30. Hogan, P. G., Chen, L., Nardone, J., and Rao, A. (2003) Transcriptional regulation by calcium, calcineurin, and NFAT. Genes Dev. 17, 2205-2232 (Pubitemid 37128637)
31. Müller, M. R., and Rao, A. (2010) NFAT, immunity and cancer. A transcription factor comes of age. Nat. Rev. Immunol. 10, 645-656
32. Luo, C., Shaw, K. T., Raghavan, A., Aramburu, J., Garcia-Cozar, F., Perrino, B. A., Hogan, P. G., and Rao, A. (1996) Interaction of calcineurin with a domain of the transcription factor NFAT1 that controls nuclear import. Proc. Natl. Acad. Sci. U.S.A. 93, 8907-8912 (Pubitemid 26281990)
33. Okamura, H., Aramburu, J., García-Rodríguez, C., Viola, J. P., Raghavan,A., Tahiliani, M., Zhang, X., Qin, J., Hogan, P. G., and Rao, A. (2000) Concerted dephosphorylation of the transcription factor NFAT1 induces a conformational switch that regulates transcriptional activity. Mol. Cell 6, 539-550
34. Abbasi, S., Lee, J. D., Su, B., Chen, X., Alcon, J. L., Yang, J., Kellems, R. E., and Xia, Y. (2006) Protein kinase-mediated regulation of calcineurin through the phosphorylation of modulatory calcineurin-interacting protein 1. J. Biol. Chem. 281, 7717-7726 (Pubitemid 43847385)
35. Hilioti, Z., Gallagher, D. A., Low-Nam, S. T., Ramaswamy, P., Gajer, P., Kingsbury, T. J., Birchwood, C. J., Levchenko, A., and Cunningham, K. W. (2004) GSK-3 kinases enhance calcineurin signaling by phosphorylation of RCNs. Genes Dev. 18, 35-47 (Pubitemid 38090686)
36. Fuentes, J. J., Genescá, L., Kingsbury, T. J., Cunningham, K. W., Pérez-Riba, M., Estivill, X., and de la Luna, S. (2000) DSCR1, overexpressed in Down syndrome, is an inhibitor of calcineurin-mediated signaling pathways. Hum. Mol. Genet. 9, 1681-1690 (Pubitemid 30427005)
37. Abbasi, S., Su, B., Kellems, R. E., Yang, J., and Xia, Y. (2005) The essential role of MEKK3 signaling in angiotensin II-induced calcineurin/nuclear factor of activated T-cells activation. J. Biol. Chem. 280, 36737-36746 (Pubitemid 41587753)
38. Sanna, B., Brandt, E. B., Kaiser, R. A., Pfluger, P., Witt, S. A., Kimball, T. R., van Rooij, E., De Windt, L. J., Rothenberg, M. E., Tschop, M. H., Benoit, S. C., and Molkentin, J. D. (2006) Modulatory calcineurin- interacting proteins 1 and 2 function as calcineurin facilitators in vivo. Proc. Natl. Acad. Sci. U.S.A. 103, 7327-7332 (Pubitemid 43727832)
39. Tsatsanis, C., Patriotis, C., Bear, S. E., and Tsichlis, P. N. (1998) The Tpl-2 protooncoprotein activates the nuclear factor of activated T cells and induces interleukin 2 expression in T cell lines. Proc. Natl. Acad. Sci. U.S.A. 95, 3827-3832 (Pubitemid 28173214)
40. de Gregorio, R., Iñiguez, M. A., Fresno, M., and Alemany, S. (2001) Cot kinase induces cyclooxygenase-2 expression in T cells through activation of the nuclear factor of activated T cells. J. Biol. Chem. 276, 27003-27009
41. Rainio, E. M., Sandholm, J., and Koskinen, P. J. (2002) Cutting edge. Transcriptional activity of NFATc1 is enhanced by the Pim-1 kinase. J. Immunol. 168, 1524-1527 (Pubitemid 34135742)
42. Ortega-Pérez, I., Cano, E., Were, F., Villar, M., Vázquez, J., and Redondo, J. M. (2005) c-Jun N-terminal kinase (JNK) positively regulates NFATc2 transactivation through phosphorylation within the N-terminal regulatory domain. J. Biol. Chem. 280, 20867-20878 (Pubitemid 40776792)
43. Gómez-Casero, E., San-Antonio, B., Iñiguez, M. A., and Fresno, M. (2007) Cot/Tpl2 and PKCζ cooperate in the regulation of the transcriptional activity of NFATc2 through the phosphorylation of its amino-terminal domain. Cell. Signal. 19, 1652-1661 (Pubitemid 46935422)
44. Okamura, H., Garcia-Rodriguez, C., Martinson, H., Qin, J., Virshup, D. M., and Rao, A. (2004) A conserved docking motif for CK1 binding controls the nuclear localization of NFAT1. Mol. Cell. Biol. 24, 4184-4195 (Pubitemid 41070992)
45. Beals, C. R., Sheridan, C. M., Turck, C. W., Gardner, P., and Crabtree, G. R. (1997) Nuclear export of NF-ATc enhanced by glycogen synthase kinase-3. Science 275, 1930-1934
46. Duque, J., Fresno, M., and Iñiguez, M. A. (2005) Expression and function of the nuclear factor of activated T cells in colon carcinoma cells. Involvement in the regulation of cyclooxygenase-2. J. Biol. Chem. 280, 8686-8693 (Pubitemid 40409556)
47. Iñiguez, M. A., Martinez-Martinez, S., Punzón, C., Redondo, J. M., and Fresno, M. (2000) An essential role of the nuclear factor of activated T cells in the regulation of the expression of the cyclooxygenase-2 gene in human T lymphocytes. J. Biol. Chem. 275, 23627-23635 (Pubitemid 30624647)
48. Jauliac, S., López-Rodriguez, C., Shaw, L. M., Brown, L. F., Rao, A., and Toker, A. (2002) The role of NFAT transcription factors in integrin-mediated carcinoma invasion. Nat. Cell Biol. 4, 540-544 (Pubitemid 34752442)
49. Corral, R. S., Iñiguez, M. A., Duque, J., López- Pérez, R., and Fresno, M. (2007) Bombesin induces cyclooxygenase-2 expression through the activation of the nuclear factor of activated T cells and enhances cell migration in Caco-2 colon carcinoma cells, Oncogene 26, 958-969
50. Yiu, G. K., and Toker, A. (2006) NFAT induces breast cancer cell invasion by promoting the induction of cyclooxygenase-2. J. Biol. Chem. 281, 12210-12217 (Pubitemid 43855303)
51. Sihto, H., Lundin, J., Lundin, M., Lehtimäki, T., Ristimäki, A., Holli, K., Sailas, L., Kataja, V., Turpeenniemi-Hujanen, T., Isola, J., Heikkilä, P., and Joensuu, H. (2011) Breast cancer biological subtypes and protein expression predict for the preferential distant metastasis sites. A nationwide cohort study. Breast Cancer Res. 13, R87
52. Kim, H. S., Moon, H. G., Han, W., Yom, C. K., Kim, W. H., Kim, J. H., and Noh, D. Y. (2012) COX2 overexpression is a prognostic marker for Stage III breast cancer. Breast Cancer Res. Treat. 132, 51-59
53. Bos, P. D., Zhang, X. H., Nadal, C., Shu, W., Gomis, R. R., Nguyen, D. X., Minn, A. J., van de Vijver, M. J., Gerald, W. L., Foekens, J. A., and Massagué, J. (2009) Genes that mediate breast cancer metastasis to the brain, Nature 459, 1005-1009
54. Singh, B., Berry, J. A., Shoher, A., and Lucci, A. (2006) COX-2 induces IL-11 production in human breast cancer cells. J. Surg. Res. 131, 267-275
55. Vázquez-Cedeira, M., Barcia-Sanjurjo, I., Sanz-García, M., Barcia, R., andLazo, P. A. (2011) Differential inhibitor sensitivity between human kinases VRK1 and VRK2. PLoS ONE 6, e23235
56. Bergmann, C., Strauss, L., Zeidler, R., Lang, S., and Whiteside, T. L. (2007) Expansion of human T regulatory type 1 cells in the microenvironment of cyclooxygenase 2 overexpressing head and neck squamous cell carcinoma. Cancer Res. 67, 8865-8873 (Pubitemid 47437463)
57. Tuynman, J. B., Vermeulen, L., Boon, E. M., Kemper, K., Zwinderman, A. H., Peppelenbosch, M. P., and Richel, D. J. (2008) Cyclooxygenase-2 inhibition inhibits c-Met kinase activity and Wnt activity in colon cancer. Cancer Res. 68, 1213-1220 (Pubitemid 351272241)
58. Ogunwobi, O. O., Wang, T., Zhang, L., and Liu, C. (2012) Cyclooxygenase-2 and Akt mediate multiple growth-factor-induced epithelial-mesenchymal transition in human hepatocellular carcinoma. J. Gastroenterol. Hepatol. 27, 566-578
59. Flockhart, R. J., Armstrong, J. L., Reynolds, N. J., and Lovat, P. E. (2009) NFAT signalling is a novel target of oncogenic BRAF in metastatic melanoma. Br. J. Cancer 101, 1448-1455
60. Diehn, M., Alizadeh, A. A., Rando, O. J., Liu, C. L., Stankunas, K., Botstein, D., Crabtree, G. R., and Brown, P. O. (2002) Genomic expression programs and the integration of the CD28 costimulatory signal in T cell activation. Proc. Natl. Acad. Sci. U.S.A. 99, 11796-11801 (Pubitemid 34994478)
61. Vinogradova, Y., Coupland, C., and Hippisley-Cox, J. (2011) Exposure to cyclooxygenase-2 inhibitors and risk of cancer. Nested case-control studies. Br. J. Cancer 105, 452-459
62. Li, Z., Schem, C., Shi, Y. H., Medina, D., and Zhang, M. (2008) Increased COX2 expression enhances tumor-induced osteoclastic lesions in breast cancer bone metastasis. Clin. Exp. Metastasis 25, 389-400 (Pubitemid 351748983)
63. Singh, B., Berry, J. A., Shoher, A., Ayers, G. D., Wei, C., and Lucci, A. (2007) COX-2 involvement in breast cancer metastasis to bone. Oncogene 26, 3789-3796 (Pubitemid 46878131)
64. Fedorov, O., Sundström, M., Marsden, B., and Knapp, S. (2007) Insights for the development of specific kinase inhibitors by targeted structural genomics. Drug Discov. Today 12, 365-372 (Pubitemid 46636375)
65. Zhang, J., Yang, P. L., and Gray, N. S. (2009) Targeting cancer with small molecule kinase inhibitors. Nat. Rev. Cancer 9, 28-39
66. Singh, B., Berry, J. A., Vincent, L. E., and Lucci, A. (2006) Involvement of IL-8 in COX-2-mediated bone metastases from breast cancer. J. Surg. Res. 134, 44-51 (Pubitemid 43866829)
67. Singh, B., Berry, J. A., Shoher, A., Ramakrishnan, V., and Lucci, A. (2005) COX-2 overexpression increases motility and invasion of breast cancer cells. Int. J. Oncol. 26, 1393-1399
68. Scheeff, E. D., Eswaran, J., Bunkoczi, G., Knapp, S., and Manning, G. (2009) Structure of the pseudokinase VRK3 reveals a degraded catalytic site, a highly conserved kinase fold, and a putative regulatory binding site. Structure 17, 128-138