Sphingosine 1-phosphate interacts with Survivin pathway to enhance tumorigenesis in cancer cells

Document Type: Original Article

Authors

1 Research Center for Pharmaceutical Nanotechnology, Tabriz University of Medical Sciences, Tabriz, Iran Department of Medical Biotechnology, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran Student Research Center Committee, Tabriz university of Medical Sciences, Tabriz, Iran

2 Medical Genetics Department, Faculty of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran

3 Research Center for Pharmaceutical Nanotechnology, Tabriz University of Medical Sciences, Tabriz, Iran Department of Medical Biotechnology, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran

Abstract

Objective(s):Degradation of sphingosine 1-phosphate (S1P), as a bioactive lipid, or deregulation of its production involves in tumor progression, metastasis and chemoresistance. Since the tumor progression effects of S1P and its mechanism in chronic lymphoblastic leukemia and non-small cell lung cancer is not fully understood, we investigated the role and one of the mechanisms of S1P in tumor progression of SKW3 and H1299 cells.
Materials and Methods: The effects of S1P on proliferation, invasion and migration was studied using MTT assay, soft-agar colony forming assay and trans-well migration assay, respectively. In order to find out the mechanisms of S1P action, the role of S1P on expression of Survivin gene was assessed by real-time RT-PCR.
Results:Our results demonstrated that although invasion was shown only in H1299 cells, low concentration of S1P, especially at 1 μM, mediated proliferation and migration in both cell lines. In addition, these effects of S1P in tumor progression are S1P receptor-dependent, and Survivin plays a key role in S1P tumorigenesis.
Conclusion:Our results confirmed the involvement of S1P and its receptors in tumor progression of SKW3 and H1299. We also investigated another mechanism of S1P involved in cell survival, tumor progression, and Survivin signaling. In conclusion, data demonstrated the importance of this molecule as a target for designing new anticancer drugs such as anti-S1P monoclonal antibody for inhibiting major downstream signaling, which plays significant role in tumorigenesis.

Keywords


1. Chalfant CE, Spiegel S. Sphingosine 1-phosphate and ceramide 1-phosphate: expanding roles in cell signaling. J Cell Sci 2005; 118:4605-4612.

2. Hannun YA, Obeid LM. Principles of bioactive lipid signaling: lessons from sphingolipids. Nat Rev Mol Cell Biol 2008; 9:139-150.

3. Goparaju SK, Jolly PS, Watterson KR, Bektas M, Alvarez S, Sarkar S, et al. The S1P2 receptor negatively regulates platelet-derived growth factor-induced motility and proliferation. Mol Cell Biol 2005; 25:4237-4249.

4. Hla T, Brinkmann V. Sphingosine 1-phosphate (S1P) Physiology and the effects of S1P receptor modulation. Neurology 2011; 76:S3-S8.

5. Jung B and Hla T. Sphingosin 1-phosphate (S1P) receptors. In: Chun J, Hla T, Spiegel s, Moolenaar W, editors. Lysophospholipid Receptors: Signaling and Biochemistry. 1st ed. John Wiley & Sons Inc; 2013.p.41-60.

6. Tabasinezhad M, Samadi N, Ghanbari P, Mohseni M, Saei AA, Sharifi S, et al. Sphingosin 1-phosphate contributes in tumor progression. J Cancer Res Ther 2013; 9:556-563.

7. Windh RT, Lee MJ, Hla T, An S, Barr AJ, Manning DR. Differential coupling of the sphingosine 1-phosphate receptors Edg-1, Edg-3, and H218/Edg-5 to the Gi, Gq, and G12 families of heterotrimeric G proteins. J Bio Chem 1999; 274:27351-27358.

8. Gangoiti P, Camacho L, Arana L, Ouro A, Granado MH, Brizuela L, et al. Control of metabolism and signaling of simple bioactive sphingolipids: Implications in disease. Prog Lipid Res 2010; 49:316-334.

9. Alvarez S.E, Milstien S, Spiegel S. Autocrine and paracrine roles of sphingosine-1-phosphate. Trends Endocrinol Metab 2007; 18:300-307.

10. Maceyka M, Harikumar KB, Milstien S, Spiegel S. Sphingosine-1-phosphate signaling and its role in disease. Trends Cell Biol 2012; 22:50-60.

11. Oskeritzian CA, Milstien S, Spiegel S. Sphingosine-1-phosphate in allergic responses, asthma and anaphylaxis. Pharmacol Ther 2007; 115:390-399.

12. Salas A, Ponnusamy S, Senkal CE, Meyers-Needham M, Selvam SP, Saddoughi SA, et al. Sphingosine kinase-1 and sphingosine 1-phosphate receptor 2 mediate Bcr-Abl1 stability and drug resistance by modulation of protein phosphatase 2A. Blood 2011; 117:5941-5952.

13. Ambrosini G, Adida C, Altieri DC. A novel anti-apoptosis gene, survivin, expressed in cancer and lymphoma. Nat Med 1997; 3:917-921.

14. Tamm I, Wang Y, Sausville E, Scudiero DA, Vigna N, Oltersdorf T, et al. IAP-family protein survivin inhibits caspase activity and apoptosis induced by Fas (CD95), Bax, caspases, and anticancer drugs. Cancer Res 1998; 58:5315-5320.

15. Li S, Chai L, Cai Z, Jin L, Chen Y, Wu H, et al. Expression of Survivin and Caspase 3 in Oral Squamous Cell Carcinoma and Peritumoral Tissue. Asian Pac J Cancer Prev 2012; 13:5027-5031.

16. Zhang1 M, Sun YF, Luo S. Ani-survivin DNAzymes inhibit cell proliferation and migration in Breast Cancer Cell Line MCF-7. Asian Pac J Cancer Prev 2012; 13: 6233-37.

17. Srivastava AK, Singh PK, Srivastava K, Singh D, Dalela D, Rath SK, et al. Diagnostic role of survivin in urinary bladder cancer. Asian Pac J Cancer Prev 2013; 14: 81-85.

18. Cho GS, Ahn TS, Jeong D, Kim JJ, Kim CJ, Cho HD,      et al. Expression of the survivin-2B splice variant related to the progression of colorectal carcinoma. J Korean Surg Soc 2011; 80:404-411.

19. Brinkmann V. Sphingosine 1-phosphate receptors in health and disease: mechanistic insights from gene deletion studies and reverse pharmacology. Pharmacol Ther 2007; 115:84-105.

20. Novgorodov AS, El-Alwani M, Bielawski J, Obeid LM, Gudz TI. Activation of sphingosine-1-phosphate receptor S1P5 inhibits oligodendrocyte progenitor migration. FASEB J 2007; 21:1503-1514.

21. Rosen H, Sanna MG, Cahalan SM, Gonzalez-Cabrera PJ. Tipping the gatekeeper: S1P regulation of endothelial barrier function. Trends Immunol 2007; 28:102-107.

22. Kluk MJ, Hla T. Signaling of sphingosine-1-phosphate via the S1P/EDG-family of G-protein-coupled receptors. Biochim Biophys Acta 2002; 1582:72-80.

23. Takuwa Y. Subtype-specific differential regulation of Rho family G proteins and cell migration by the Edg family sphingosine-1-phosphate receptors. Biochim Biophys Acta 2002; 1582:112-120.

24. Okajima F, Tomura H, Sho K, Nochi H, Tamoto K, Kondo Y. Involvement of pertussis toxin-sensitive GTP-binding proteins in sphingosine 1-phosphate-induced activation of phospholipase Cî—¸ Ca< sup> 2+</sup> system in HL60 leukemia cells. FEBS lett 1996; 379:260-264.

25. Yoshida Y, Nakada M, Sugimoto N, Harada T, Hayashi Y, Kita D, et al. Sphingosine‐1‐phosphate receptor type 1 regulates glioma cell proliferation and correlates with patient survival. Int J Cancer 2010; 126:2341-2352.

26. Huang YL, Huang WP, Lee H. Roles of sphingosine 1-phosphate on tumorigenesis. World J Biol Chem 2011; 2:25-34.

27. Yamashita H, Kitayama J, Shida D, Yamaguchi H, Mori K, Osada M, et al, Sphingosine 1-phosphate receptor expression profile in human gastric cancer cells: differential regulation on the migration and proliferation. J Surg Res 2006; 130:80-87.

28. Kluk MJ, Ryan KP, Wang B, Zhang G, Rodig SJ, Sanchez T. Sphingosine-1-phosphate receptor 1 in classical Hodgkin lymphoma: assessment of expression and role in cell migration. Lab Invest 2013; 93:462-471.

29. Park KS, Kim MK, Lee HY, Kim SD, Lee SY, Kim JM, et al. S1P stimulates chemotactic migration and invasion in OVCAR3 ovarian cancer cells. Biochem Biophys Res Commun 2007; 356:239-44.

30. Gandy KAO, Adada M, Canals D, Carroll B, Roddy P, Hannun YA, et al. Epidermal growth factor-induced cellular invasion requires sphingosine-1-phosphate/sphingosine-1-phosphate 2 receptor-mediated ezrin activation. FASEB J 2013; 27:3155-3166.

31. Van Brocklyn JR. Regulation of cancer cell migration and invasion by sphingosine-1-phosphate. World J Biol Chem 2010; 1:307.

32. Maceyka M, Payne SG, Milstien S, Spiegel S. Sphingosine kinase, sphingosine-1-phosphate, and apoptosis. Biochim Biophys Acta 2002; 1585:193-201.

33. Cuvillier O, Levade T. Sphingosine 1-phosphate antagonizes apoptosis of human leukemia cells by inhibiting release of cytochrome c and Smac/DIABLO from mitochondria. Blood 2001; 98:2828-2836.

34. Pyne NJ, Pyne S. Sphingosine 1-phosphate and cancer. Nat Rev Cancer 2010; 10:489-503.

35. McNeish I, Lopes R, Bell S, McKay T, Fernandez M, Lockley M, et al. Survivin interacts with Smac/DIABLO in ovarian carcinoma cells but is redundant in Smac-mediated apoptosis. Exp Cell Res 2005; 302:69-82.

36. Ling X, Bernacki RJ, Brattain MG, Li F. Induction of survivin expression by taxol (paclitaxel) is an early
event, which is independent of taxol-mediated G2/M arrest. J Biol Chem 2004; 279:15196-15203.

37. Zhao P, Meng Q, Liu L-Z, You Y-P, Liu N, Jiang B-H. Regulation of survivin by PI3K/Akt/p70S6K1 pathway. Biochem Biophys Res Commun 2010; 395:219-224.

38. Shi M, Zhang H, Li M, Xue J, Fu Y, Yan L, et al. Normal endometrial stromal cells regulate survival and apoptosis signaling through PI3K/AKt/Survivin pathway in endometrial adenocarcinoma cells< i> in vitro</i>. Gynecol Oncol 2011; 123:387-392.