Sphingosine Kinase 1 Overexpression Contributes to Cetuximab Resistance in Human Colorectal Cancer Models(672 views) Rosa R, Marciano R, Malapelle U, Formisano L, Nappi L, D'Amato C, D'Amato V, Damiano V, Marf G, Del Vecchio S, Zannetti A, Greco A, De Stefano A, Carlomagno C, Veneziani BM, Troncone G, De Placido S, Bianco R
Clin Cancer Res (ISSN: 1078-0432, 1078-0432linking, 1078-0432print), 2013 Jan 1; 19(1): 138-147.
Keywords: Cetuximab, Fingolimod, N Dimethylsphingosine, Small Interfering Rna, Sphingosine Kinase 1, Animal Experiment, Animal Model, Animal Tissue, Apoptosis, Article, Cancer Cell Culture, Cancer Inhibition, Cancer Patient, Cancer Resistance, Cancer Tissue, Colorectal Cancer, Controlled Study, Drug Response, Drug Sensitivity, Enzyme Activation, Enzyme Inhibition, Gene Silencing, Human, Human Cell, Human Tissue, Immunohistochemistry, In Vitro Study, In Vivo Study, Mouse, Nonhuman, Nucleotide Sequence, Priority Journal, Protein Expression, Signal Transduction, Survival Time, Treatment Duration, Tumor Xenograft, Antibodies, Monoclonal, Humanized, Antineoplastic Agents, Cell Line, Colorectal Neoplasms, Disease Models, Drug Resistance, Gene Expression, Phosphotransferases (alcohol Group Acceptor), Propylene Glycols, Receptors, Lysosphingolipid, Treatment Outcome, Xenograft Model Antitumor Assays, Humanized Pharmacology Therapeutic Use, Antineoplastic Agents Pharmacology Therapeutic Use, Colorectal Neoplasms Drug Therapy Genetics Metabolism, Neoplasm Drug Effects Genetics, Phosphotransferases (alcohol Group Acceptor) Genetics Metabolism, Propylene Glycols Pharmacology, Lysosphingolipid Antagonists, Inhibitors, Sphingosine Analogs, Derivatives Pharmacology,
Affiliations: *** IBB - CNR ***
Cattedra di Oncologia Medica, Dipartimento di Endocrinologia e Oncologia Molecolare e Clinica, Universitàdi Napoli Federico II, Via S. Pansini, 5, 80131 Napoli, Italy
Scienze Biomorfologiche e Funzionali, Università di Napoli Federico II, Naples, Italy
Institute of Biostructures and Bioimages, National Research Council, Naples, Italy
CEINGE, Biotecnologie Avanzate, Naples, Italy
Dipartimento di Biologia e Patologia Cellulare e Molecolare L. Califano, Università di Napoli Federico II, Naples, Italy
Dipartimento di Medicina Sperimentale e Scienze Biochimiche, Università di Roma Tor Vergata, Rome, Italy
Dipartimenti di Endocrinologia ed Oncologia Molecolare e Clinica, Universita di Napoli Federico II, Napoli, Italy.
References: Bardelli, A., Siena, S., Molecular mechanisms of resistance to cetuximab and panitumumab in colorectal cancer (2010) J Clin Oncol, 28, pp. 1254-126
Wheeler, D.L., Dunn, E.F., Harari, P.M., Understanding resistance to EGFR inhibitors-impact on future treatment strategies (2010) Nat Rev Clin Oncol, 7, pp. 493-507
Sartore-Bianchi, A., Bencardino, K., Cassingena, A., Venturini, F., Funaioli, C., Cipani, T., Therapeutic implications of resistance to molecular therapies in metastatic colorectal cancer (2010) Cancer Treat Rev, 36 S, pp. S1-S5
Fyrst, H., Saba, J.D., An update on sphingosine-1-phosphate and other sphingolipid mediators (2010) Nat Chem Biol, 6, pp. 489-497
Taha, T.A., Hannun, Y.A., Obeid, L.M., Sphingosine kinase: Biochemical and cellular regulation and role in disease (2006) J Biochem Mol Biol, 39, pp. 113-131
Vadas, M., Xia, P., McCaughan, G., Gamble, J., The role of sphingosine kinase 1 in cancer: Oncogene or non-oncogene addiction? (2008) Biochim Biophys Acta, 1781, pp. 442-447
Cuvillier, O., Ader, I., Bouquerel, P., Brizuela, L., Malavaud, B., Mazerolles, C., Activation of sphingosine kinase-1 in cancer: Implications for therapeutic targeting (2010) Curr Mol Pharmacol, 3, pp. 53-65
Pyne, S., Bittman, R., Pyne, N.J., Sphingosine kinase inhibitors and cancer: Seeking the golden sword of Hercules (2011) Cancer Res, 71, pp. 6576-6582
Baran, Y., Salas, A., Senkal, C.E., Gunduz, U., Bielawski, J., Obeid, L.M., Alterations of ceramide/sphingosine 1-phosphate rheostat involved in the regulation of resistance to imatinib-induced apoptosis in K562 human chronic myeloid leukemia cells (2007) J Biol Chem, 282, pp. 10922-10934
Bektas, M., Johnson, S.P., Poe, W.E., Bigner, D.D., Friedman, H.S., A sphingosine kinase inhibitor induces cell death in temozolomide resistant glioblastoma cells (2009) Cancer Chemother Pharmacol, 64, pp. 1053-1058
Guillermet-Guibert, J., Davenne, L., Pchejetski, D., Saint-Laurent, N., Brizuela, L., Guilbeau-Frugier, C., Targeting the sphingolipid metabolism to defeat pancreatic cancer cell resistance to the chemotherapeutic gemcitabine drug (2009) Mol Cancer Ther, 8, pp. 809-820
Sauer, L., Nunes, J., Salunkhe, V., Skalska, L., Kohama, T., Cuvillier, O., Sphingosine kinase 1 inhibition sensitizes hormone-resistant prostate cancer to docetaxel (2009) Int J Cancer, 125, pp. 2728-2736
Watson, C., Long, J.S., Orange, C., Tannahill, C.L., Mallon, E., McGlynn, L.M., High expression of sphingosine 1-phosphate receptors, S1P1 and S1P3, sphingosine kinase 1, and extracellular signal-regulated kinase-1/2 is associated with development of tamoxifen resistance in estrogen receptor-positive breast cancer patients (2010) Am J Pathol, 177, pp. 2205-2215
Marfe, G., Di Stefano, C., Gambacurta, A., Ottone, T., Martini, V., Abruzzese, E., Sphingosine kinase 1 overexpression is regulated by signaling through PI3K, AKT2, and mTOR in imatinib-resistant chronic myeloid leukemia cells (2011) Exp Hematol, 39, pp. 653-665
Shida, D., Fang, X., Kordula, T., Takabe, K., Lépine, S., Alvarez, S.E., Cross-talk between LPA1 and epidermal growth factor receptors mediates upregulation of sphingosine kinase 1 to promote gastric cancer cell motility and invasion (2008) Cancer Res, 68, pp. 6569-6577
Paugh, B.S., Paugh, S.W., Bryan, L., Kapitonov, D., Wilczynska, K.M., Gopalan, S.M., EGF regulates plasminogen activator inhibitor-1 (PAI-1) by a pathway involving c-Src, PKCdelta, and sphingosine kinase 1 in glioblastoma cells (2008) FASEB J, 22, pp. 455-465
Bianco, R., Rosa, R., Damiano, V., Daniele, G., Gelardi, T., Garofalo, S., Vascular endothelial growth factor receptor-1 contributes to resistance to anti-epidermal growth factor receptor drugs in human cancer cells (2008) Clin Cancer Res, 14, pp. 5069-5080
Venkataraman, K., Thangada, S., Michaud, J., Oo, M.L., Ai, Y., Lee, Y.M., Extracellular export of sphingosine kinase-1a contributes to the vascular S1P gradient (2006) Biochem J, 397, pp. 461-471
Cho, S.Y., Lee, H.J., Jeong, S.J., Lee, H.J., Kim, H.S., Chen, C.Y., Sphingosine kinase 1 pathway is involved in melatonin-induced HIF-1α inactivation in hypoxic PC-3 prostate cancer cells (2011) J Pineal Res, 51, pp. 87-93
Guan, H., Song, L., Cai, J., Huang, Y., Wu, J., Yuan, J., Sphingosine kinase 1 regulates the Akt/FOXO3a/Bim pathway and contributes to apoptosis resistance in glioma cells (2011) PLoS ONE, 6, pp. e19946
Bao, M., Chen, Z., Xu, Y., Zhao, Y., Zha, R., Huang, S., Sphingosine kinase 1 promotes tumour cell migration and invasion via the S1P/EDG1 axis in hepatocellular carcinoma (2012) Liver Int, 32, pp. 331-338
Ratajczak, M.Z., Lee, H., Wysoczynski, M., Wan, W., Marlicz, W., Laughlin, M.J., Novel insight into stem cell mobilization-plasma sphingosine-1-phosphate is a major chemoattractant that directs the egress of hematopoietic stem progenitor cells from the bone marrow and its level in peripheral blood increases during mobilization due to activation of complement cascade/membrane attack complex (2010) Leukemia, 24, pp. 976-985
Rosa, R., Melisi, D., Damiano, V., Bianco, R., Garofalo, S., Gelardi, T., Toll-like receptor 9 agonist IMO cooperates with cetuximab in K-ras mutant colorectal and pancreatic cancers (2011) Clin Cancer Res, 17, pp. 6531-6541
Pan, J., Tao, Y.F., Zhou, Z., Cao, B.R., Wu, S.Y., Zhang, Y.L., An novel role of sphingosine kinase-1 (SPHK1) in the invasion and metastasis of esophageal carcinoma (2011) J Transl Med, 9, p. 157
Bordeaux, J., Welsh, A., Agarwal, S., Killiam, E., Baquero, M., Hanna, J., Antibody validation (2010) Biotechniques, 48, pp. 197-209
Liska, D., Chen, C.T., Bachleitner-Hofmann, T., Christensen, J.G., Weiser, M.R., HGF rescues colorectal cancer cells from EGFR inhibition via MET activation (2011) Clin Cancer Res, 17, pp. 472-482
Nemoto, S., Nakamura, M., Osawa, Y., Kono, S., Itoh, Y., Okano, Y., Sphingosine kinase isoforms regulate oxaliplatin sensitivity of human colon cancer cells through ceramide accumulation and Akt activation (2009) J Biol Chem, 284, pp. 10422-10432
Brinkmann, V., Billich, A., Baumruker, T., Heining, P., Schmouder, R., Francis, G., Fingolimod (FTY720): Discovery and development of an oral drug to treat multiple sclerosis (2010) Nat Rev Drug Discov, 9, pp. 883-897
Pchejetski, D., Bohler, T., Brizuela, L., Sauer, L., Doumerc, N., Golzio, M., FTY720 (fingolimod) sensitizes prostate cancer cells to radiotherapy by inhibition of sphingosine kinase-1 (2010) Cancer Res, 70, pp. 8651-8661
Li, C.X., Shao, Y., Ng, K.T., Liu, X.B., Ling, C.C., Ma, Y.Y., FTY720 suppresses liver tumor metastasis by reducing the population of circulating endothelial progenitor cells (2012) PLoS One, 7, pp. e32380
Sukocheva, O., Wadham, C., Holmes, A., Albanese, N., Verrier, E., Feng, F., Estrogen transactivates EGFR via the sphingosine 1-phosphate receptor Edg-3: The role of sphingosine kinase-1 (2006) J Cell Biol, 173, pp. 301-310
Pitson, S.M., Moretti, P.A., Zebol, J.R., Lynn, H.E., Xia, P., Vadas, M.A., Activation of sphingosine kinase 1 by ERK1/2-mediated phosphorylation (2003) EMBO J, 22, pp. 5491-5500
Kim, J.W., Kim, Y.W., Inagaki, Y., Hwang, Y.A., Mitsutake, S., Ryu, Y.W., Synthesis and evaluation of sphingoid analogs as inhibitors of sphingosine kinases (2005) Bioorg Med Chem, 13, pp. 3475-3485
Kapitonov, D., Allegood, J.C., Mitchell, C., Hait, N.C., Almenara, J.A., Adams, J.K., Targeting sphingosine kinase 1 inhibits Akt signaling, induces apoptosis, and suppresses growth of human glioblastoma cells and xenografts (2009) Cancer Res, 69, pp. 6915-6923
Bonnaud, S., Niaudet, C., Legoux, F., Corre, I., Delpon, G., Saulquin, X., Sphingosine-1-phosphate activates the AKT pathway to protect small intestines from radiation-induced endothelial apoptosis (2010) Cancer Res, 70, pp. 9905-9915
Song, L., Xiong, H., Li, J., Liao, W., Wang, L., Wu, J., Sphingosine kinase-1 enhances resistance to apoptosis through activation of PI3K/Akt/NF-κB pathway in human non-small cell lung cancer (2011) Clin Cancer Res, 17, pp. 1839-1849
Takabe, K., Paugh, S.W., Milstien, S., Spiegel, S., "Inside-out" signaling of sphingosine-1-phosphate: Therapeutic targets (2008) Pharmacol Rev, 60, pp. 181-195
Spiegel, S., Milstien, S., The outs and the ins of sphingosine-1-phosphate in immunity (2011) Nat Rev Immunol, 11, pp. 403-415
Tonelli, F., Lim, K.G., Loveridge, C., Long, J., Pitson, S.M., Tigyi, G., FTY720 and (S)-FTY720 vinylphosphonate inhibit sphingosine kinase 1 and promote its proteasomal degradation in human pulmonary artery smooth muscle, breast cancer and androgen-independent prostate cancer cells (2010) Cell Signal, 22, pp. 1536-1542
Kawamori, T., Kaneshiro, T., Okumura, M., Maalouf, S., Uflacker, A., Bielawski, J., Role for sphingosine kinase 1 in colon carcinogenesis (2009) FASEB J, 23, pp. 405-414
Wheeler, D. L., Dunn, E. F., Harari, P. M., Understanding resistance to EGFR inhibitors-impact on future treatment strategies (2010) Nat Rev Clin Oncol, 7, pp. 493-507
Taha, T. A., Hannun, Y. A., Obeid, L. M., Sphingosine kinase: Biochemical and cellular regulation and role in disease (2006) J Biochem Mol Biol, 39, pp. 113-131
Paugh, B. S., Paugh, S. W., Bryan, L., Kapitonov, D., Wilczynska, K. M., Gopalan, S. M., EGF regulates plasminogen activator inhibitor-1 (PAI-1) by a pathway involving c-Src, PKCdelta, and sphingosine kinase 1 in glioblastoma cells (2008) FASEB J, 22, pp. 455-465
Cho, S. Y., Lee, H. J., Jeong, S. J., Lee, H. J., Kim, H. S., Chen, C. Y., Sphingosine kinase 1 pathway is involved in melatonin-induced HIF-1 inactivation in hypoxic PC-3 prostate cancer cells (2011) J Pineal Res, 51, pp. 87-93
Ratajczak, M. Z., Lee, H., Wysoczynski, M., Wan, W., Marlicz, W., Laughlin, M. J., Novel insight into stem cell mobilization-plasma sphingosine-1-phosphate is a major chemoattractant that directs the egress of hematopoietic stem progenitor cells from the bone marrow and its level in peripheral blood increases during mobilization due to activation of complement cascade/membrane attack complex (2010) Leukemia, 24, pp. 976-985
Pan, J., Tao, Y. F., Zhou, Z., Cao, B. R., Wu, S. Y., Zhang, Y. L., An novel role of sphingosine kinase-1 (SPHK1) in the invasion and metastasis of esophageal carcinoma (2011) J Transl Med, 9, p. 157
Li, C. X., Shao, Y., Ng, K. T., Liu, X. B., Ling, C. C., Ma, Y. Y., FTY720 suppresses liver tumor metastasis by reducing the population of circulating endothelial progenitor cells (2012) PLoS One, 7, pp. e32380
Pitson, S. M., Moretti, P. A., Zebol, J. R., Lynn, H. E., Xia, P., Vadas, M. A., Activation of sphingosine kinase 1 by ERK1/2-mediated phosphorylation (2003) EMBO J, 22, pp. 5491-5500
Kim, J. W., Kim, Y. W., Inagaki, Y., Hwang, Y. A., Mitsutake, S., Ryu, Y. W., Synthesis and evaluation of sphingoid analogs as inhibitors of sphingosine kinases (2005) Bioorg Med Chem, 13, pp. 3475-3485
Sphingosine Kinase 1 Overexpression Contributes to Cetuximab Resistance in Human Colorectal Cancer Models
Purpose: Although the anti-EGF receptor (EGFR) monoclonal antibody cetuximab is an effective strategy in colorectal cancer therapy, its clinical use is limited by intrinsic or acquired resistance. Alterations in the "sphingolipid rheostat"-the balance between the proapoptotic molecule ceramide and the mitogenic factor sphingosine-1-phosphate (S1P)-due to sphingosine kinase 1 (SphK1) overactivation have been involved in resistance to anticancer-targeted agents. Moreover, cross-talks between SphK1 and EGFR-dependent signaling pathways have been described. Experimental design: We investigated SphK1 contribution to cetuximab resistance in colorectal cancer, in preclinical in vitro/in vivo models, and in tumor specimens from patients. Results: SphK1 was found overexpressed and overactivated in colorectal cancer cells with intrinsic or acquired resistance to cetuximab. SphK1 contribution to resistance was supported by the demonstration that SphK1 inhibition by N,N-dimethyl-sphingosine or silencing via siRNA in resistant cells restores sensitivity to cetuximab, whereas exogenous SphK1 overexpression in sensitive cells confers resistance to these agents. Moreover, treatment of resistant cells with fingolimod (FTY720), a S1P receptor (S1PR) antagonist, resulted in resensitization to cetuximab both in vitro and in vivo, with inhibition of tumor growth, interference with signal transduction, induction of cancer cells apoptosis, and prolongation of mice survival. Finally, a correlation between SphK1 expression and cetuximab response was found in colorectal cancer patients. Clin Cancer Res; 19(1); 138-47. (c) 2012 AACR.
Sphingosine Kinase 1 Overexpression Contributes to Cetuximab Resistance in Human Colorectal Cancer Models
Petraglia F, Singh AA, Carafa V, Nebbioso A, Conte M, Scisciola L, Valente S, Baldi A, Mandoli A, Petrizzi VB, Ingenito C, De Falco S, Cicatiello V, Apicella I, Janssen-megens EM, Kim B, Yi G, Logie C, Heath S, Ruvo M, Wierenga ATJ, Flicek P, Yaspo ML, Della Valle V, Bernard O, Tomassi S, Novellino E, Feoli A, Sbardella G, Gut I, Vellenga E, Stunnenberg HG, Mai A, Martens JHA, Altucci L * Combined HAT/EZH2 modulation leads to cancer-selective cell death(284 views) Oncotarget (ISSN: 1949-2553electronic, 1949-2553linking), 2018 May 22; 9(39): 25630-25646. Impact Factor:5.008 ViewExport to BibTeXExport to EndNote