Browse > Article
http://dx.doi.org/10.4062/biomolther.2016.228

Sphingosylphosphorylcholine Induces Thrombospondin-1 Secretion in MCF10A Cells via ERK2  

Kang, June Hee (College of Pharmacy, Dongguk University)
Kim, Hyun Ji (College of Pharmacy, Dongguk University)
Park, Mi Kyung (College of Pharmacy, Dongguk University)
Lee, Chang Hoon (College of Pharmacy, Dongguk University)
Publication Information
Biomolecules & Therapeutics / v.25, no.6, 2017 , pp. 625-633 More about this Journal
Abstract
Sphingosylphosphorylcholine (SPC) is one of the bioactive phospholipids that has many cellular functions such as cell migration, adhesion, proliferation, angiogenesis, and $Ca^{2+}$ signaling. Recent studies have reported that SPC induces invasion of breast cancer cells via matrix metalloproteinase-3 (MMP-3) secretion leading to WNT activation. Thrombospondin-1 (TSP-1) is a matricellular and calcium-binding protein that binds to a wide variety of integrin and non-integrin cell surface receptors. It regulates cell proliferation, migration, and apoptosis in inflammation, angiogenesis and neoplasia. TSP-1 promotes aggressive phenotype via epithelial mesenchymal transition (EMT). The relationship between SPC and TSP-1 is unclear. We found SPC induced EMT leading to mesenchymal morphology, decrease of E-cadherin expression and increases of N-cadherin and vimentin. SPC induced secretion of thrombospondin-1 (TSP-1) during SPC-induced EMT of various breast cancer cells. Gene silencing of TSP-1 suppressed SPC-induced EMT as well as migration and invasion of MCF10A cells. An extracellular signal-regulated kinase inhibitor, PD98059, significantly suppressed the secretion of TSP-1, expressions of N-cadherin and vimentin, and decrease of E-cadherin in MCF10A cells. ERK2 siRNA suppressed TSP-1 secretion and EMT. From online PROGgene V2, relapse free survival is low in patients having high TSP-1 expressed breast cancer. Taken together, we found that SPC induced EMT and TSP-1 secretion via ERK2 signaling pathway. These results suggests that SPC-induced TSP-1 might be a new target for suppression of metastasis of breast cancer cells.
Keywords
Sphingosylphosphorylcholine; Thrombospondin-1; Epithelial mesenchymal transition; ERK2;
Citations & Related Records
Times Cited By KSCI : 6  (Citation Analysis)
연도 인용수 순위
1 Kurokawa, T., Yumiya, Y., Fujisawa, H., Shirao, S., Kashiwagi, S., Sato, M., Kishi, H., Miwa, S., Mogami, K., Kato, S., Akimura, T., Soma, M., Ogasawara, K., Ogawa, A., Kobayashi, S. and Suzuki, M. (2009) Elevated concentrations of sphingosylphosphorylcholine in cerebrospinal fluid after subarachnoid hemorrhage: a possible role as a spasmogen. J. Clin. Neurosci. 16, 1064-1068.   DOI
2 Lawler, J. W., Slayter, H. S. and Coligan, J. E. (1978) Isolation and characterization of a high molecular weight glycoprotein from human blood platelets. J. Biol. Chem. 253, 8609-8616.
3 Lee, H. Y., Lee, S. Y., Kim, S. D., Shim, J. W., Kim, H. J., Jung, Y. S., Kwon, J. Y., Baek, S. H., Chung, J. and Bae, Y. S. (2011) Sphingosylphosphorylcholine stimulates CCL2 production from human umbilical vein endothelial cells. J. Immunol. 186, 4347-4353.   DOI
4 Lim, S. C., Lee, K. M. and Kang, T. J. (2015) Chitin from cuttlebone activates inflammatory cells to enhance the cell migration. Biomol. Ther. (Seoul) 23, 333-338.   DOI
5 Park, M. K., You, H. J., Lee, H. J., Kang, J. H., Oh, S. H., Kim, S. Y. and Lee, C. H. (2013) 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
6 Valastyan, S. and Weinberg, R. A. (2011) Tumor metastasis: molecular insights and evolving paradigms. Cell 147, 275-292.   DOI
7 Sid, B., Langlois, B., Sartelet, H., Bellon, G., Dedieu, S. and Martiny, L. (2008) Thrombospondin-1 enhances human thyroid carcinoma cell invasion through urokinase activity. Int. J. Biochem. Cell Biol. 40, 1890-1900.   DOI
8 Sorensen, K. P., Thomassen, M., Tan, Q., Bak, M., Cold, S., Burton, M., Larsen, M. J. and Kruse, T. A. (2013) Long non-coding RNA HOTAIR is an independent prognostic marker of metastasis in estrogen receptor-positive primary breast cancer. Breast Cancer Res. Treat. 142, 529-536.   DOI
9 Tiwari, N., Gheldof, A., Tatari, M. and Christofori, G. (2012) EMT as the ultimate survival mechanism of cancer cells. Semin. Cancer Biol. 22, 194-207.   DOI
10 Wang, X., Zhu, Y., Ma, Y., Wang, J., Zhang, F., Xia, Q. and Fu, D. (2013) The role of cancer stem cells in cancer metastasis: new perspective and progress. Cancer Epidemiol. 37, 60-63.   DOI
11 Wang, Y., Klijn, J. G., Zhang, Y., Sieuwerts, A. M, Look, M. P., Yang, F., Talantov, D., Timmermans, M., Meijer-van Gelder, M. E., Yu, J., Jatkoe, T., Berns, E. M., Atkins, D. and Foekens, J. A. (2005) Gene-expression profiles to predict distant metastasis of lymph-node-negative primary breast cancer. Lancet 365, 671-679.   DOI
12 Xiao, Y. J., Schwartz, B., Washington, M., Kennedy, A., Webster, K., Belinson, J. and Xu, Y. (2001) Electrospray ionization mass spectrometry analysis of lysophospholipids in human ascitic fluids: comparison of the lysophospholipid contents in malignant vs nonmalignant ascitic fluids. Anal. Biochem. 290, 302-313.   DOI
13 Xu, Y. (2002) Sphingosylphosphorylcholine and lysophosphatidylcholine: G protein-coupled receptors and receptor-mediated signal transduction. Biochim. Biophys. Acta 1582, 81-88.   DOI
14 Zheng, M., Zhang, X., Min, C., Choi, B. G., Oh, I. J. and Kim, K. M. (2016) Functional regulation of dopamine D3 receptor through interaction with PICK1. Biomol. Ther. (Seoul) 24, 475-481.   DOI
15 Xu, Y., Zhu, K., Hong, G., Wu, W., Baudhuin, L. M., Xiao, Y. and Damron, D. S., (2000) Sphingosylphosphorylcholine is a ligand for ovarian cancer G-protein-coupled receptor 1. Nat. Cell Biol. 2, 261-267.   DOI
16 Yang, C. R., Wei, Y., Qi, S. T., Chen L., Zhang, Q. H., Ma J. Y., Luo Y. B., Wang Y. P., Hou, Y., Schatten, H., Liu, Z. H. and Sun, Q. Y. (2012) The G protein coupled receptor 3 is involved in cAMP and cGMP signaling and maintenance of meiotic arrest in porcine oocytes, PLoS ONE 7, e38807.   DOI
17 Yee, K. O., Connolly, C. M., Duquette, M., Kazerounian, S., Washington, R. and Lawler, J. (2009) The effect of thrombospondin-1 on breast cancer metastasis. Breast Cancer Res. Treat. 114, 85-96.   DOI
18 Zhu, K., Baudhuin, L. M., Hong, G., Williams, F. S., Cristina, K. L., Kabarowski, J. H., Witte, O. N. and Xu, Y. (2001) Sphingosylphosphorylcholine and lysophosphatidylcholine are ligands for the G protein-coupled receptor GPR4. J. Biol. Chem. 276, 41325-41335.   DOI
19 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
20 Adams, J. C. and Tucker, R. P. (2000) The thrombospondin type 1 repeat (TSR) superfamily: diverse proteins with related roles in neuronal development. Dev. Dyn. 218, 280-299.   DOI
21 Boguslawski, G., Lyons, D., Harvey, K. A., Kovala, A. T. and English, D. (2000) Sphingosylphosphorylcholine induces endothelial cell migration and morphogenesis. Biochem. Biophys. Res. Commun. 272, 603-609.   DOI
22 Park, K. S., Kim, H. K, Lee, J. H., Choi, Y. B., Park, S. Y., Yang, S. H., Kim, S. Y. and Hong, K. M. (2010) Transglutaminase 2 as a cisplatin resistance marker in non-small cell lung cancer. J. Cancer Res. Clin. Oncol. 136, 493-502.   DOI
23 Kim, H. J., Kang, G. J., Kim, E. J., Park, M. K., Byun, H. J., Nam, S., Lee, H. and Lee, C. H. (2016) Novel effects of sphingosylphosphorylcholine on invasion of breast cancer: Involvement of matrix metalloproteinase-3 secretion leading to WNT activation. Biochim. Biophys. Acta 1862, 1533-1543.   DOI
24 Meyer zu Heringdorf, D., Himmel, H. M. and Jakobs, K. H. (2002) Sphingosylphosphorylcholine-biological functions and mechanisms of action. Biochim. Biophys. Acta 1582, 178-189.   DOI
25 Murphy-Ullrich, J. E. and Poczatek, M. (2000) Activation of latent TGF-beta by thrombospondin-1: mechanisms and physiology. Cytokine Growth Factor Rev. 11, 59-69.   DOI
26 Nieto, M. A., Huang, R. Y., Jackson, R. A. and Thiery, J. P. (2016) EMT: 2016. Cell 166, 21-45.   DOI
27 Nixon, G. F., Mathieson, F. A. and Hunter, I. (2008) The multi-functional role of sphingosylphosphorylcholine. Prog. Lipid Res. 47, 62-75.   DOI
28 Retraction (2006) Sphingosylphosphorylcholine is a ligand for ovarian cancer G-protein-coupled receptor 1. Nat. Cell Biol. 8, 299.
29 Park, M. K., Park, S., Kim, H. J., Kim, E. J., Kim, S. Y., Kang, G. J., Byun, H. J., Kim, S. H., Lee, H. and Lee, C. H. (2016) Novel effects of FTY720 on perinuclear reorganization of keratinnetwork induced by sphingosylphosphorylcholine: Involvement of protein phosphatase 2A and G-protein-coupled receptor-12. Eur. J. Pharmacol. 775, 86-95.   DOI
30 Retraction (2005) Sphingosylphosphorylcholine and lysophosphatidylcholine are ligands for the G protein-coupled receptor GPR4. J. Biol. Chem. 280, 43280.
31 Schlyer, S. and Horuk, R. (2006) I want a new drug: G-protein-coupled receptors in drug development. Drug Discov. Today 11, 481-493.   DOI
32 Schultz-Cherry, S., Lawler, J. and Murphy-Ullrich, J. E. (1994) The type 1 repeats of thrombospondin 1 activate latent transforming growth factor-${\beta}$. J. Biol. Chem. 269, 26783-26788.
33 Seufferlein, T. and Rozengurt, E. (1995) Sphingosylphosphorylcholine rapidly induces tyrosine phosphorylation of p125FAK and paxillin, rearrangement of the actin cytoskeleton and focal contact assembly. Requirement of p21rho in the signaling pathway. J. Biol. Chem. 270, 24343-24351.   DOI
34 Shin, S. and Blenis, J. (2010) ERK2/Fra1/ZEB pathway induces epithelial-to-mesenchymal transition. Cell Cycle 9, 2483-2484.   DOI
35 Shin, S., Dimitri, C. A., Yoon, S. O., Dowdle, W. and Blenis, J. (2010) ERK2 but not ERK1 induces epithelial-to-mesenchymal transformation via DEF motif-dependent signaling events. Mol. Cell 38, 114-127.   DOI
36 De, U., Kundu, S., Patra, N., Ahn, M. Y., Ahn, J. H., Son, J. Y., Yoon, J. H., Moon, H. R., Lee, B. M. and Kim, H. S. (2015) A new histone deacetylase inhibitor, MHY219, inhibits the migration of human prostate cancer cells via HDAC1. Biomol. Ther. (Seoul) 23, 434-441.   DOI
37 Calcerrada, M. C., Miguel, B. G., Catalan, R. E. and Martinez, A. M. (1999) Sphingosylphosphorylcholine increases calcium concentration in isolated brain nuclei. Neurosci. Res. 33, 229-232.   DOI
38 Campone, M., Valo, I., Jezequel, P., Moreau, M., Boissard, A., Campion, L., Loussouarn, D., Verriele, V., Coqueret, O. and Guette, C. (2015) Prediction of recurrence and survival for triple-negative breast cancer (TNBC) by a protein signature in tissue samples. Mol. Cell Proteomics 14, 2936-2946.   DOI
39 Cao, Z., Shang, B., Zhang, G., Miele, L., Sarkar, F. H., Wang, Z. and Zhou, Q. (2013) Tumor cell-mediated neovascularization and lymphangiogenesis contrive tumor progression and cancer metastasis. Biochim. Biophys. Acta 1836, 273-286.
40 Eccles, S. A. and Welch, D. R. (2007) Metastasis: recent discoveries and novel treatment strategies. Lancet 369, 1742-1757.   DOI
41 Farhan, H. and Rabouille, C. (2011) Signalling to and from the secretory pathway. J. Cell Sci. 124, 171-180.   DOI
42 Ghajar, C. M., Peinado, H., Mori, H., Matei, I. R., Evason, K. J., Brazier, H., Almeida, D., Koller, A., Hajjar, K. A., Stainier, D. Y., Chen, E. I., Lyden, D. and Bissell, M. J. (2013) The perivascular niche regulates breast tumour dormancy. Nat. Cell Biol. 15, 807-817.   DOI
43 Firlej, V., Mathieu, J. R., Gilbert, C., Lemonnier, L., Nakhle, J., Gallou-Kabani, C., Guarmit, B., Morin, A., Prevarskaya, N., Delongchamps, N. B. and Cabon, F. (2011) Thrombospondin-1 triggers cell migration and development of advanced prostate tumors. Cancer Res. 71, 7649-7658.   DOI
44 Fosu-Mensah, N., Peris, M.S., Weeks, H.P., Cai, J. and Westwell, A.D. (2015) Advances in small-molecule drug discovery for triple-negative breast cancer. Future Med. Chem. 7, 2019-2039.   DOI
45 Foulkes, W. D., Smith, W. D. and Reis-Filho, J. S. (2010) Triple-negative breast cancer. N. Engl. J. Med. 363, 1938-1948.   DOI
46 Goswami, C. P. and Nakshatri, H. (2014) PROGgeneV2: enhancements on the existing database. BMC Cancer 14, 970.   DOI
47 Horiguchi, H., Yamagata, S., Rong Qian, Z., Kagawa, S. and Sakashita, N. (2013) Thrombospondin-1 is highly expressed in desmoplastic components of invasive ductal carcinoma of the breast and associated with lymph node metastasis. J. Med. Invest. 60, 91-96.   DOI
48 Ignatov, A., Lintzel, J., Hermans-Borgmeyer, I., Kreienkamp, H. J., Joost P., Thomsen, S., Methner, A. and Schaller, H. C. (2003) Role of the G-protein-coupled receptor GPR12 as highaffinityreceptor for sphingosylphosphorylcholine and its expression and functionin brain development. J. Neurosci. 23, 907-914.   DOI
49 Im, D. S. (2003) Linking Chinese medicine and G-protein-coupled receptors. Trends Pharmacol. Sci. 24, 2-4.   DOI
50 Jayachandran, A., Anaka, M., Prithviraj, P., Hudson, C., McKeown, S. J., Lo, P. H., Vella, L. J., Goding, C. R., Cebon, J. and Behren, A. (2014) Thrombospondin 1 promotes an aggressive phenotype through epithelial-to-mesenchymal transition in human melanoma. Oncotarget 5, 5782-5797.
51 Jeon, E. S., Moon, H. J., Lee, M. J., Song, H. Y., Kim, Y. M., Bae, Y. C., Jung, J. S. and Kim, J. H. (2006) Sphingosylphosphorylcholine induces differentiation of human mesenchymal stem cells into smooth-muscle-like cells through a TGF-beta-dependent mechanism. J. Cell Sci. 119, 4994-5005.   DOI
52 Jeong, Y. H., Park, J. S., Kim, D. H. and Kim, H.-S. (2016) Lonchocarpine increases Nrf2/ARE-mediated antioxidant enzyme expression by modulating AMPK and MAPK signaling in brain astrocytes. Biomol. Ther. (Seoul) 24, 581-588.   DOI
53 Jimenez, B., Volpert, O. V., Crawford, S. E., Febbraio, M., Silverstein, R. L. and Bouck, N. (2000) Signals leading to apoptosis-dependent inhibition of neovascularization by thrombospondin-1. Nat. Med. 6, 41-48.   DOI
54 Kalluri, R. and Weinberg, R. A. (2009) The basics of epithelial-mesenchymal transition. J. Clin. Invest. 119, 1420-1428.   DOI
55 Kim, E. J., Kim, H. J., Park, M. K., Kang, G. J., Byun, H. J., Lee, H. and Lee, C. H. (2015) Cardamonin suppresses TGF-${\beta}1$-induced epithelial mesenchymal transition via restoring protein phosphatase 2A expression. Biomol. Ther. (Seoul) 23, 141-148.   DOI
56 Kim, H. J., Choi, W. J. and Lee, C. H. (2015) Phosphorylation and reorganization of keratin networks: Implications for carcinogenesis and epithelial mesenchymal transition. Biomol. Ther. (Seoul) 23, 301-312.   DOI