Browse > Article
http://dx.doi.org/10.4062/biomolther.2013.066

Ethacrynic Acid Inhibits Sphingosylphosphorylcholine-Induced Keratin 8 Phosphorylation and Reorganization via Transglutaminase-2 Inhibition  

Byun, Hyun Jung (College of Pharmacy, Dongguk University)
Kang, Kyung Jin (College of Pharmacy, Dongguk University)
Park, Mi Kyung (College of Pharmacy, Dongguk University)
Lee, Hye Ja (College of Pharmacy, Dongguk University)
Kang, June Hee (College of Pharmacy, Dongguk University)
Lee, Eun Ji (College of Pharmacy, Dongguk University)
Kim, You Ri (College of Pharmacy, Dongguk University)
Kim, Hyun Ji (College of Pharmacy, Dongguk University)
Kim, Young Woo (College of Pharmacy, Dongguk University)
Jung, Kyung Chae (National Cancer Center)
Kim, Soo Youl (National Cancer Center)
Lee, Chang Hoon (College of Pharmacy, Dongguk University)
Publication Information
Biomolecules & Therapeutics / v.21, no.5, 2013 , pp. 338-342 More about this Journal
Abstract
Sphingosylphosphorylcholine (SPC) is significantly increased in the malicious ascites of tumor patients and induces perinuclear reorganization of keratin 8 (K8) filaments in PANC-1 cells. The reorganization contributes to the viscoelasticity of metastatic cancer cells resulting in increased migration. Recently, we reported that transglutaminase-2 (Tgase-2) is involved in SPC-induced K8 phosphorylation and reorganization. However, effects of Tgase-2 inhibitors on SPC-induced K8 phosphorylation and reorganization were not clearly studied. We found that ethacrynic acid (ECA) concentration-dependently inhibited Tgase-2. Therefore, we examined the effects of ECA on SPC-induced K8 phosphorylation and reorganization. ECA concentration-dependently suppressed the SPC-induced phosphorylation and perinuclear reorganization of K8. ECA also suppressed the SPC-induced migration and invasion. SPC induced JNK activation through Tgase-2 expression and ECA suppressed the activation and expression of JNK in PANC-1 cells. These results suggested that ECA might be useful to control Tgase-2 dependent metastasis of cancer cells such as pancreatic cancer and lung cancers.
Keywords
Sphingosylphosphorylcholine; Transglutaminase-2; Keratin-8 phosphorylation and reorganization; Ethacrynic acid; Migration; Invasion;
Citations & Related Records
Times Cited By KSCI : 1  (Citation Analysis)
연도 인용수 순위
1 Park, M. K., Park, Y., Shim, J., Lee, H. J., Kim, S. and Lee, C. H. (2012) Novel involvement of leukotriene B(4) receptor 2 through ERK activation by PP2A down-regulation in leukotriene B(4)-induced keratin phosphorylation and reorganization of pancreatic cancer cells. Biochim. Biophys. Acta 1823, 2120-2129.   DOI   ScienceOn
2 Park, M. K., You, H. J., Lee, H. J., Kang, J. H., Oh, S. H., Kim, S. Y. and Lee, C. H. (2013b) Transglutaminase-2 induces N-cadherin expression in TGF-beta1-induced epithelial mesenchymal transition via c-Jun-N-terminal kinase activation by protein phosphatase 2A down-regulation. Eur. J. Cancer 49, 1692-1705.   DOI   ScienceOn
3 Rolli, C. G., Seufferlein, T., Kemkemer, R. and Spatz, J. P. (2010) Impact of tumor cell cytoskeleton organization on invasiveness and migration: a microchannel-based approach. PLoS One 5, e8726.   DOI   ScienceOn
4 Suresh, S. (2007) Biomechanics and biophysics of cancer cells. Acta Biomater. 3, 413-438.   DOI   ScienceOn
5 Steeg, P. S. (2006) Tumor metastasis: mechanistic insights and clinical challenges. Nat. Med. 12, 895-904.   DOI   ScienceOn
6 Valastyan, S. and Weinberg, R. A. (2011) Tumor metastasis: molecular insights and evolving paradigms. Cell 147, 275-292.   DOI   ScienceOn
7 Verma, A., Wang, H., Manavathi, B., Fok, J. Y., Mann, A. P., Kumar, R. and Mehta, K. (2006) Increased expression of tissue transglutaminase in pancreatic ductal adenocarcinoma and its implications in drug resistance and metastasis. Cancer Res. 66, 10525-10533.   DOI   ScienceOn
8 Vivas, L. and Chiaraviglio, E. (1989) Central effect of agents which alter sodium transport on water drinking in the rat. Brain Res. Bull. 22, 201-206.   DOI   ScienceOn
9 Wall, G. C., Bigner, D. and Craig, S. (2003) Ethacrynic acid and the sulfa-sensitive patient. Arch. Intern. Med. 163, 116-117.   DOI   ScienceOn
10 Kim, S. Y. (2011) Transglutaminase 2: a new paradigm for NF-kappaB involvement in disease. Adv. Enzymol. Relat. Areas Mol. Biol. 78, 161-195.
11 Ku, N. O., Azhar, S. and Omary, M. B. (2002) Keratin 8 phosphorylation by p38 kinase regulates cellular keratin filament reorganization: modulation by a keratin 1-like disease causing mutation. J. Biol. Chem. 277, 10775-10782.   DOI   ScienceOn
12 Li, R. and El-Mallakh, R. S. (2004) Differential response of bipolar and normal control lymphoblastoid cell sodium pump to ethacrynic acid. J. Affect. Disord. 80, 11-17.   DOI   ScienceOn
13 Lai, T. S., Liu, Y., Tucker, T., Daniel, K. R., Sane, D. C., Toone, E., Burke, J. R., Strittmatter, W. J. and Greenberg, C. S. (2008) Identification of chemical inhibitors to human tissue transglutaminase by screening existing drug libraries. Chem. Biol. 15, 969-978.   DOI   ScienceOn
14 Lee, K. N., Arnold, S. A., Birckbichler, P. J., Patterson, M. K., Jr., Fraij, B. M., Takeuchi, Y. and Carter, H. A. (1993) Site-directed mutagenesis of human tissue transglutaminase: Cys-277 is essential for transglutaminase activity but not for GTPase activity. Biochim. Biophys. Acta 1202, 1-6.   DOI   ScienceOn
15 Lee, S. H., Kim, N., Kim, S. J., Song, J., Gong, Y. D. and Kim, S. Y. (2013) Anti-cancer effect of a quinoxaline derivative GK13 as a transglutaminase 2 inhibitor. J. Cancer Res. Clin. Oncol. 139, 1279-1294.   DOI   ScienceOn
16 Mhaouty-Kodja, S. (2004) Ghalpha/tissue transglutaminase 2: an emerging G protein in signal transduction. Biol. Cell 96, 363-367.   DOI
17 Park, M. K., Jo, S. H., Lee, H. J., Kang, J. H., Kim, Y. R., Kim, H. J., Lee, E. J., Koh, J. Y., Ahn, K. O., Jung, K. C., Oh, S. H., Kim, S. Y. and Lee, C. H. (2013a) Novel suppressive effects of cardamonin on the activity and expression of transglutaminase-2 lead to blocking the migration and invasion of cancer cells. Life Sci. 92, 154-160.   DOI   ScienceOn
18 Park, M. K., Lee, H. J., Shin, J., Noh, M., Kim, S. Y. and Lee, C. H. (2011) Novel participation of transglutaminase-2 through c-Jun N-terminal kinase activation in sphingosylphosphorylcholine-induced keratin reorganization of PANC-1 cells. Biochim. Biophys. Acta 1811, 1021-1029.   DOI   ScienceOn
19 Bordeleau, F., Bessard, J., Sheng, Y. and Marceau, N. (2008) Keratin contribution to cellular mechanical stress response at focal adhesions as assayed by laser tweezers. Biochem. Cell Biol. 86, 352-359.   DOI
20 Beil, M., Micoulet, A., von Wichert, G., Paschke, S., Walther, P., Omary, M. B., Van Veldhoven, P. P., Gern, U., Wolff-Hieber, E., Eggermann, J., Waltenberger, J., Adler, G., Spatz, J. and Seufferlein, T. (2003) Sphingosylphosphorylcholine regulates keratin network architecture and visco-elastic properties of human cancer cells. Nat. Cell Biol. 5, 803-811.   DOI   ScienceOn
21 Busch, T., Armacki, M., Eiseler, T., Joodi, G., Temme, C., Jansen, J., von Wichert, G., Omary, M. B., Spatz, J. and Seufferlein, T. (2012) Keratin 8 phosphorylation regulates keratin reorganization and migration of epithelial tumor cells. J. Cell Sci. 125, 2148-2159.   DOI
22 Cheng, C. C., Liu, Y. H., Ho, C. C., Chao, W. T., Pei, R. J., Hsu, Y. H., Yeh, K. T., Ho, L. C., Tsai, M. C. and Lai, Y. S. (2008) The influence of plectin deficiency on stability of cytokeratin18 in hepatocellular carcinoma. J. Mol. Histol. 39, 209-216.   DOI   ScienceOn
23 Chhabra, A., Verma, A. and Mehta, K. (2009) Tissue transglutaminase promotes or suppresses tumors depending on cell context. Anticancer Res. 29, 1909-1919.
24 Cross, S. E., Jin, Y. S., Rao, J. and Gimzewski, J. K. (2007) Nanomechanical analysis of cells from cancer patients. Nat. Nanotechnol. 2, 780-783.   DOI   ScienceOn
25 Han, Y., Englert, J. A., Delude, R. L. and Fink, M. P. (2005) Ethacrynic acid inhibits multiple steps in the NF-kappaB signaling pathway. Shock 23, 45-53.   DOI   ScienceOn
26 Kim, K. M., Noh, M. S., Kim, S. H., Park, M. K., Lee, H. J., Kim, S. Y. and Lee, C. H. (2010) Ethacrynic acid and citral suppressed the all trans retinoid-induced monocyte chemoattractant protein-1 production in human dermal fibroblasts. Biomol. Ther. 18, 71-76.   과학기술학회마을   DOI   ScienceOn