BMB Reports

생화학분자생물학회 (Korean Society for Biochemistry and Molecular Biology)
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Depletion of Neuroguidin/CANu1 sensitizes human osteosarcoma U2OS cells to doxorubicin

  • 투고 : 2010.10.13
  • 심사 : 2010.12.01
  • 발행 : 2011.01.31
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초록

Osteosarcoma is a primary bone cancer which occurs mainly in children. Neuroguidin/CANu1 is a nucleolar protein involved in the maintenance of ribosomal structure. In this study, we investigated the effect of Neuroguidin/CANu1 depletion on the response of osteosarcoma cells to doxorubicin. In normal circumstances, Neuroguidin/CANu1 is localized at nucleoli, which translocates to nuclear foci in the presence of doxorubicin. shRNA knockdown of Neuroguidin/CANu1 did not affect cell viability in the absence of doxorubicin, but led to enhanced cytotoxicity in doxorubicin-treated cells. Doxorubicin increased the population of apoptotic cells by 3-fold in Neuroguidin/CANu1-depleted cells compared to that in control cells. Depletion of Neuroguidin/CANu1 mRNA induced the expression of p21 and the cleavage of PARP, leading to increased caspase-3/7 activity. Together, these results suggest that Neuroguidin/CANu1 is required for maintaining cellular homeostasis and may contribute to the improved efficiency of chemotherapy.

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참고문헌

  1. Daw, N. C., Billups, C. A., Rodriguez-Galinodo, C., McCarville M. B., Rao, B. N., Cain, A. M., Jenkins, J. J., Neel, M. D. and Meyer W. H. (2006) Metastatic osteosarcoma. Cancer 106, 403-412. https://doi.org/10.1002/cncr.21626
  2. Bielack, S. S., Kempf-Bielack, B., Delling, G., Exner, G. U., Flege, S., Helmke, K., Kotz, R., Salzer-Kuntschik, M., Werner, M., Winkelmann, W., Zoubek, A., Jurgens, H. and Winkler, K. (2002) Prognostic factors in high-grade osteosarcoma of the extremities or trunk: an analysis of 1,702 patients treated on neoadjuvant cooperative osteosarcoma study group protocols. J. Clin. Oncol. 20, 776-790. https://doi.org/10.1200/JCO.20.3.776
  3. Niswander, L. M. and Kim, S. Y. (2010) Stratifying osteosarcoma: minimizing and maximizing therapy. Curr. Oncol. Rep. 12, 266-270. https://doi.org/10.1007/s11912-010-0106-3
  4. Orosco, A., Fromigue, O., Bazille, C., Entz-Werle, N., Levillain, P., Marie, P. J. and Modrowski, D. (2007) Syndecan-2 affects the basal and chemotherapy-induced apoptosis in osteosarcoma. Cancer Res. 67, 3708-3715. https://doi.org/10.1158/0008-5472.CAN-06-4164
  5. Sihn, C. R., Lee, Y. S., Jeong, J. S., Park, K. and Kim, S. H. (2008) CANu1, a novel nucleolar protein, accumulated on centromere in response to DNA damage. Genes Cells 13, 787-796. https://doi.org/10.1111/j.1365-2443.2008.01205.x
  6. Jung, M. Y., Lorenz, L. and Richter, J. D. (2006) Translational control by neuroguidin, a eukaryotic initiation factor 4E and CPEB binding protein. Mol. Cell Biol. 26, 4277-4287. https://doi.org/10.1128/MCB.02470-05
  7. Tembe, V. and Henderson, B. R. (2007) Protein trafficking in response to DNA damage. Cell Signal 19, 1113-1120. https://doi.org/10.1016/j.cellsig.2007.03.001
  8. Mo, Y. Y., Yu, Y., Shen, Z. and Beck, W. T. (2002) Nucleolar delocalization of human topoisomerase I in response to topotecan correlates with sumoylation of the protein. J. Biol. Chem. 277, 2958-2964. https://doi.org/10.1074/jbc.M108263200
  9. Daniely, Y., Dimitrova, D. D. and Borowiec, J. A. (2002) Stress-dependent nucleolin mobilization mediated by p53-nucleolin complex formation. Mol. Cell Biol. 22, 6014-6022. https://doi.org/10.1128/MCB.22.16.6014-6022.2002
  10. Blander, G., Zalle, N., Daniely, Y., Taplick, J., Gray, M. D. and Oren, M. (2002) DNA damage-induced translocation of the Werner helicase is regulated by acetylation. J. Biol. Chem. 277, 50934-50940. https://doi.org/10.1074/jbc.M210479200
  11. Condemine, W., Takahashi, Y. and Le, B. M. (2007) A nucleolar targeting signal in PML-I addresses PML to nucleolar caps in stressed or senescent cells. J. Cell Sci. 120, 3219-3227. https://doi.org/10.1242/jcs.007492
  12. Kurki, S., Latonen, L. and Laiho, M. (2003) Cellular stress and DNA damage invoke temporally distinct Mdm2, p53 and PML complexes and damage-specific nuclear relocalization. J. Cell Sci. 116, 3917-3925. https://doi.org/10.1242/jcs.00714
  13. Alastalo, T. P., Hellesuo, M., Sandqvist, A., Hietakangas, V., Kallio, M. and Sistonen, L. (2003) Formation of nuclear stress granules involves HSF2 and coincides with the nucleolar localization of Hsp70. J. Cell Sci. 116, 3557-3570. https://doi.org/10.1242/jcs.00671
  14. Yuan, X. W., Zhu, X. F., Huang, X. F., Sheng, P. Y., He, A. S., Yang, Z. B., Deng, R., Feng, G. K. and Liao, W. M. (2007) Interferon-alpha enhances sensitivity of human osteosarcoma U2OS cells to doxorubicin by p53-dependent apoptosis. Acta Pharmacol. Sin. 28, 1835-1841. https://doi.org/10.1111/j.1745-7254.2007.00662.x
  15. Bruland, O. S. and Pihl, A. (1997) On the current management of osteosarcoma. A critical evaluation and a proposal for a modified treatment strategy. Eur. J. Cancer 33, 1725-1731. https://doi.org/10.1016/S0959-8049(97)00252-9
  16. Lambert, L. A., Qiao, N., Hunt, K. K., Lambert, D. H., Mills, G. B., Meijer, L. and Keyomarsi, K. (2008) Autophagy: a novel mechanism of synergistic cytotoxicity between doxorubicin and roscovitine in a sarcoma model. Cancer Res. 68, 7966-7974. https://doi.org/10.1158/0008-5472.CAN-08-1333
  17. Zucchi, R. and Danesi, R. (2003) Cardiac toxicity of antineoplastic anthracyclines. Curr. Med. Chem. Anticancer Agents 3, 151-171. https://doi.org/10.2174/1568011033353434
  18. Schimmel, K. J., Richel, D. J., van den Brink, R. B. and Guchelaar, H. J. (2004) Cardiotoxicity of cytotoxic drugs. Cancer Treat. Rev. 30, 181-191. https://doi.org/10.1016/j.ctrv.2003.07.003
  19. Liu, S., Bishop, W. R. and Liu, M. (2003) Differential effects of cell cycle regulatory protein p21(WAF1/Cip1) on apoptosis and sensitivity to cancer chemotherapy. Drug Resist. Updat. 6, 183-195. https://doi.org/10.1016/S1368-7646(03)00044-X
  20. Agrawal, S., Agarwal, M. L., Chatterjee-Kishore, M., Stark, G. R. and Chisolm, G. M. (2002) Stat1-dependent, p53-independent expression of p21(waf1) modulates oxysterolinduced apoptosis. Mol. Cell Biol. 22, 1981-1992. https://doi.org/10.1128/MCB.22.7.1981-1992.2002
  21. Teraishi, F., Kadowaki, Y., Tango, Y., Kawashima, T., Umeoka, T., Kagawa, S., Tanaka, N. and Fujiwara, T. (2003) Ectopic p21sdi1 gene transfer induces retinoic acid receptor beta expression and sensitizes human cancer cells to retinoid treatment. Int. J. Cancer 103, 833-839. https://doi.org/10.1002/ijc.10892
  22. Lincet, H., Poulain, L., Remy, J. S., Deslandes, E., Duigou, F., Gauduchon, P. and Staedel, C. (2000) The p21 (cip1/waf1) cyclin-dependent kinase inhibitor enhances the cytotoxic effect of cisplatin in human ovarian carcinoma cells. Cancer Lett. 161, 17-26. https://doi.org/10.1016/S0304-3835(00)00586-3
  23. Qin, L. F. and Ng, I. O. (2001) Exogenous expression of p21(WAF1/CIP1) exerts cell growth inhibition and enhances sensitivity to cisplatin in hepatoma cells. Cancer Lett. 172, 7-15. https://doi.org/10.1016/S0304-3835(01)00701-7
  24. Klibanov, S. A., O'Hagan, H. M. and Ljungman, M. (2001) Accumulation of soluble and nucleolar-associated p53 proteins following cellular stress. J. Cell Sci. 114, 1867-1873.
  25. Zhang, S., Hemmerich, P. and Grosse, F. (2004) Nucleolar localization of the human telomeric repeat binding factor 2 (TRF2). J. Cell Sci. 117, 3935-3945. https://doi.org/10.1242/jcs.01249
  26. Mayer, C. and Grummt, I. (2005) Cellular stress and nucleolar function. Cell Cycle 4, 1036-1038. https://doi.org/10.4161/cc.4.8.1925
  27. Montanaro, L., Trere, D. and Derenzini, M. (2008) Nucleolus, ribosomes, and cancer. Am. J. Pathol. 173, 301-310. https://doi.org/10.2353/ajpath.2008.070752
  28. Derenzini, M., Montanaro, L. and Trere, D. (2008) What the nucleolus says to a tumour pathologist. Histopathology 54, 753-762. https://doi.org/10.1111/j.1365-2559.2008.03168.x
  29. Meng, L., Lin, T. and Tsai, R. Y. (2008) Nucleoplasmic mobilization of nucleostemin stabilizes MDM2 and promotes G2-M progression and cell survival. J. Cell Sci. 121, 4037-4046. https://doi.org/10.1242/jcs.037952
  30. Ma, H. and Pederson, T. (2008) Nucleophosmin is a binding partner of nucleostemin in human osteosarcoma cells. Mol. Biol. Cell 19, 2870-2875. https://doi.org/10.1091/mbc.E08-02-0128
  31. Jafarnejad, S. M., Mowla, S. J. and Matin, M. M. (2008) Knocking-down the expression of nucleostemin significantly decreases rate of proliferation of rat bone marrow stromal stem cells in an apparently p53-independent manner. Cell Prolif. 41, 28-35. https://doi.org/10.1111/j.1365-2184.2007.00505.x
  32. Dai, M. S., Sun, X. X. and Lu, H. (2008) Aberrant expression of nucleostemin activates p53 and induces cell cycle arrest via inhibition of MDM2. Mol. Cell Biol. 28, 4365-4376. https://doi.org/10.1128/MCB.01662-07
  33. Woo, L. L., Futami, K., Shimamoto, A., Furuichi, Y. and Frank, K. M. (2006) The Rothmund-Thomson gene product RECQL4 localizes to the nucleolus in response to oxidative stress. Exp. Cell Res. 312, 3443-3457. https://doi.org/10.1016/j.yexcr.2006.07.023
  34. Otake, Y., Soundararajan, S., Sengupta, T. K., Kio, E. A., Smith, J. C., Pineda-Roman, M., Stuart, R. K., Spicer, E. K. and Fernandes, D. J. (2007) Overexpression of nucleolin in chronic lymphocytic leukemia cells induces stabilization of bcl2 mRNA. Blood 109, 3069-3075.
  35. Kaelin, Jr. W. G. (2005) The concept of synthetic lethality in the context of anticancer therapy. Nat. Rev. Cancer 5, 689-698. https://doi.org/10.1038/nrc1691
  36. Chan, D. A. and Giaccia, A. J. (2008) Targeting cancer cells by synthetic lethality: autophagy and VHL in cancer therapeutics. Cell Cycle 7, 2987-2990. https://doi.org/10.4161/cc.7.19.6776
  37. Bommi-Reddy, A. and Kaelin, Jr. W. G. (2010) Slaying RAS with a synthetic lethal weapon. Cell Res. 20, 119-121. https://doi.org/10.1038/cr.2010.16
  38. Kaelin, Jr. W. G. (2009) Synthetic lethality: a framework for the development of wiser cancer therapeutics. Genome Med. 1, 99. https://doi.org/10.1186/gm99
  39. Wang, Y. A., Johnson, S. K., Brown, B. L. and Dobson, P. R. (2009) Differential enhancement of the anti-cancer effect of doxorubicin by Akt inhibitors on human breast cancer cells with differing genetic backgrounds. Oncol. Rep. 21, 437-442.

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