Regulator of calcineurin 1 modulates cancer cell migration in vitro
详细信息    查看全文
  • 作者:Allan V. Espinosa (1)
    Motoo Shinohara (1)
    Leonardo M. Porchia (1)
    Yun Jae Chung (1) (2)
    Samantha McCarty (1)
    Motoyasu Saji (1)
    Matthew D. Ringel (1)
  • 关键词:Adhesion ; Calcineurin ; GPR54 ; KiSS1 ; Metastases ; Metastin ; Motility ; Thyroid Cancer
  • 刊名:Clinical & Experimental Metastasis
  • 出版年:2009
  • 出版时间:August 2009
  • 年:2009
  • 卷:26
  • 期:6
  • 页码:517-526
  • 全文大小:351KB
  • 参考文献:1. Chiang AC, Massague J (2008) Molecular basis of metastasis. N Engl J Med 359(26):2814鈥?823. doi:10.1056/NEJMra0805239 CrossRef
    2. Chambers AF, Groom AC, MacDonald IC (2002) Dissemination and growth of cancer cells in metastatic sites. Nat Rev Cancer 2(8):563鈥?72. doi:10.1038/nrc865 CrossRef
    3. Ramaswamy S, Ross KN, Lander ES et al (2003) A molecular signature of metastasis in primary solid tumors. Nat Genet 33(1):49鈥?4. doi:10.1038/ng1060 CrossRef
    4. Podsypanina K, Du YC, Jechlinger M et al (2008) Seeding and propagation of untransformed mouse mammary cells in the lung. Science 321(5897):1841鈥?844. doi:10.1126/science.1161621 CrossRef
    5. Shevde LA, Welch DR (2003) Metastasis suppressor pathways-an evolving paradigm. Cancer Lett 198(1):1鈥?0. doi:10.1016/S0304-3835(03)00304-5 CrossRef
    6. Ohtake T, Shintani Y, Honda S et al (2001) Metastasis suppressor gene KiSS-1 encodes peptide ligand of a G-protein-coupled receptor. Nature 411(6787):613鈥?17. doi:10.1038/35079135 CrossRef
    7. Kotani M, Detheux M, Vandenbogaerde A et al (2001) The metastasis suppressor gene KiSS-1 encodes kisspeptins, the natural ligands of the orphan G protein-coupled receptor GPR54. J Biol Chem 276(37):34631鈥?4636. doi:10.1074/jbc.M104847200 CrossRef
    8. Muir AI, Chamberlain L, Elshourbagy NA et al (2001) AXOR12: a novel human G protein-coupled receptor, activated by the peptide KiSS-1. J Biol Chem 276(31):28969鈥?8975. doi:10.1074/jbc.M102743200 CrossRef
    9. Lee JH, Miele ME, Hicks DJ et al (1996) KiSS-1, a novel human malignant melanoma metastasis-suppressor gene. J Natl Cancer Inst 88(23):1731鈥?737. doi:10.1093/jnci/88.23.1731 CrossRef
    10. Ringel MD, Hardy E, Bernet VJ et al (2002) Metastin receptor is overexpressed in papillary thyroid cancer and activates MAP kinase in thyroid cancer cells. J Clin Endocrinol Metab 87(5):2399鈥?402. doi:10.1210/jc.87.5.2399 CrossRef
    11. Ikeguchi M, Yamaguchi K, Kaibara N (2004) Clinical significance of the loss of KiSS-1 and orphan G-Protein-coupled receptor (hOT7T175) gene expression in esophageal squamous cell carcinoma. Clin Cancer Res 10(4):1379鈥?383. doi:10.1158/1078-0432.CCR-1519-02 CrossRef
    12. Dhar DK, Naora H, Kubota H et al (2004) Downregulation of KiSS-1 expression is responsible for tumor invasion and worse prognosis in gastric carcinoma. Int J Cancer 111(6):868鈥?72. doi:10.1002/ijc.20357 CrossRef
    13. Hori A, Honda S, Asada M et al (2001) Metastin suppresses the motility and growth of CHO cells transfected with its receptor. Biochem Biophys Res Commun 286(5):958鈥?63. doi:10.1006/bbrc.2001.5470 CrossRef
    14. Shirasaki F, Takata M, Hatta N et al (2001) Loss of expression of the metastasis suppressor gene KiSS1 during melanoma progression and its association with LOH of chromosome 6q16.3鈥搎23. Cancer Res 61(20):7422鈥?425
    15. Jiang Y, Berk M, Singh LS et al (2005) KiSS1 suppresses metastasis in human ovarian cancer via inhibition of protein Kinase C Alpha. Clin Exp Metastasis 22(5):369鈥?76. doi:10.1007/s10585-005-8186-4 CrossRef
    16. Nash KT, Phadke PA, Navenot J-M et al (2007) Requirement of KISS1 secretion for multiple organ metastasis suppression and maintenance of tumor dormancy. J Natl Cancer Inst 99(4):309鈥?21. doi:10.1093/jnci/djk053 CrossRef
    17. Stathatos N, Bourdeau I, Espinosa AV et al (2005) KiSS-1/G protein-coupled receptor 54 metastasis suppressor pathway increases myocyte-enriched calcineurin interacting protein 1 expression and chronically inhibits calcineurin activity. J Clin Endocrinol Metab 90(9):5432鈥?440. doi:10.1210/jc.2005-0963 CrossRef
    18. Fuentes JJ, Pritchard MA, Estivill X (1997) Genomic organization, alternative splicing, and expression patterns of the DSCR1 (Down syndrome candidate region 1) gene. Genomics 44(3):358鈥?61. doi:10.1006/geno.1997.4866 CrossRef
    19. Rothermel B, Vega RB, Yang J et al (2000) A protein encoded within the Down syndrome critical region is enriched in striated muscles and inhibits calcineurin signaling. J Biol Chem 275(12):8719鈥?725. doi:10.1074/jbc.275.12.8719 CrossRef
    20. Vega RB, Rothermel BA, Weinheimer CJ et al (2003) Dual roles of modulatory calcineurin-interacting protein 1 in cardiac hypertrophy. Proc Natl Acad Sci USA 100(2):669鈥?74. doi:10.1073/pnas.0237225100 CrossRef
    21. van Rooij E, Doevendans PA, Crijns HJ et al (2004) MCIP1 overexpression suppresses left ventricular remodeling and sustains cardiac function after myocardial infarction. Circ Res 94(3):e18鈥揺26. doi:10.1161/01.RES.0000118597.54416.00 CrossRef
    22. Vega RB, Yang J, Rothermel BA et al (2002) Multiple domains of MCIP1 contribute to inhibition of calcineurin activity. J Biol Chem 277(33):30401鈥?0407. doi:10.1074/jbc.M200123200 CrossRef
    23. Abbasi S, Lee J-D, Su B et al (2006) Protein kinase-mediated regulation of calcineurin through the phosphorylation of modulatory calcineurin-interacting protein 1. J Biol Chem 281(12):7717鈥?726. doi:10.1074/jbc.M510775200 CrossRef
    24. Seo SR, Chung KC (2008) CREB activates proteasomal degradation of DSCR1/RCAN1. FEBS Lett 582(13):1889鈥?893. doi:10.1016/j.febslet.2008.04.059 CrossRef
    25. Bush CR, Havens JM, Necela BM et al (2007) Functional genomic analysis reveals cross-talk between peroxisome proliferator-activated receptor gamma and calcium signaling in human colorectal cancer cells. J Biol Chem 282(32):23387鈥?3401. doi:10.1074/jbc.M702708200 CrossRef
    26. Iizuka M, Abe M, Shiiba K et al (2004) Down syndrome candidate region 1, a downstream target of VEGF, participates in endothelial cell migration and angiogenesis. J Vasc Res 41(4):334鈥?44. doi:10.1159/000079832 CrossRef
    27. Minami T, Horiuchi K, Miura M et al (2004) Vascular endothelial growth factor- and thrombin-induced termination factor, down syndrome critical region-1, attenuates endothelial cell proliferation and angiogenesis. J Biol Chem 279(48):50537鈥?0554. doi:10.1074/jbc.M406454200 CrossRef
    28. Schweppe RE, Klopper JP, Korch C et al (2008) Deoxyribonucleic acid profiling analysis of 40 human thyroid cancer cell lines reveals cross-contamination resulting in cell line redundancy and misidentification. J Clin Endocrinol Metab 83(11):4331鈥?341. doi:10.1210/jc.2008-1102 CrossRef
    29. Ringel MD (2008) 鈥淭hyroid cancer鈥?cell line misidentification: a time for proactive change. J Clin Endocrinol Metab 93(11):4226鈥?227. doi:10.1210/jc.2008-2008 CrossRef
    30. Vasko V, Saji M, Hardy E et al (2004) Akt activation and localization correlate with tumor invasion and oncogene expression in thyroid cancer. J Med Genet 41(3):161鈥?70. doi:10.1136/jmg.2003.015339 mg.2003.015339">CrossRef
    31. Hoffmann S, Maschuw K, Hassan I et al (2005) Differential pattern of integrin receptor expression in differentiated and anaplastic thyroid cancer cell lines. Thyroid 15(9):1011鈥?020. doi:10.1089/thy.2005.15.1011 CrossRef
    32. Mulero MC, Aubareda A, Orzaez M, et al. (2009) Inhibiting the calcineurin-NFAT signaling pathway with a regulator of calcineurin-derived peptide without affecting general calcineurin phosphatase activity. J biol chem [Epub ahead of print]
    33. Rinker-Schaeffer CW, O鈥橩eefe JP, Welch DR et al (2006) Metastasis suppressor proteins: discovery, molecular mechanisms, and clinical application. Clinical Cancer Research 12(13):3882鈥?889. doi:10.1158/1078-0432.CCR-06-1014 CrossRef
    34. Ryeom S, Baek K-H, Rioth MJ et al (2008) Targeted deletion of the calcineurin inhibitor DSCR1 suppresses tumor growth. Cancer Cell 13(5):420鈥?31. doi:10.1016/j.ccr.2008.02.018 CrossRef
  • 作者单位:Allan V. Espinosa (1)
    Motoo Shinohara (1)
    Leonardo M. Porchia (1)
    Yun Jae Chung (1) (2)
    Samantha McCarty (1)
    Motoyasu Saji (1)
    Matthew D. Ringel (1)

    1. Division of Endocrinology, Diabetes, and Metabolism, The Ohio State University College of Medicine and Arthur G. James Comprehensive Cancer Center, 445D McCampbell Hall, 1581 Dodd Drive, Columbus, OH, 43210, USA
    2. Division of Endocrinology and Metabolism, Department of Internal Medicine, Chung-Ang University College of Medicine, Seoul, Korea
  • ISSN:1573-7276
文摘
Metastasis suppressors and other regulators of cell motility play an important role in tumor invasion and metastases. We previously identified that activation of the G protein coupled receptor 54 (GPR54) by the metastasis suppressor metastin inhibits cell migration in association with overexpression of Regulator of calcineurin 1 (RCAN1), an endogenous regulator of calcineurin. Calcineurin inhibitors also blocked cell migration in vitro and RCAN1 protein levels were reduced in nodal metastases in thyroid cancer. The purpose of the current study was to determine directly if RCAN1 functions as a motility suppressor in vitro. Several cancer cell lines derived from different cancer types with different motility rates were evaluated for RCAN1 expression levels. Using these systems we determined that reduction of endogenous RCAN1 using siRNA resulted in an increase in cancer cell motility while expression of exogenous RCAN1 reduced cell motility. In one cell line with a high migratory rate, the stability of exogenously expressed RCAN1 protein was reduced and was rescued by treatment with a proteasome inhibitor. Finally, overexpression of RCAN1 was associated with an increase in cell adhesion to collagen IV and reduced calcineurin activity. In summary, we have demonstrated that the expression of exogenous RCAN1 reduces migration and alters adhesion; and that the loss of endogenous RCAN1 leads to an increase in migration in the examined cancer cell lines. These results are consistent with a regulatory role for RCAN1 in cancer cell motility in vitro.
NGLC 2004-2010.National Geological Library of China All Rights Reserved.
Add:29 Xueyuan Rd,Haidian District,Beijing,PRC. Mail Add: 8324 mailbox 100083
For exchange or info please contact us via email.