Therapeutic implications of bioactive sphingolipids: A focus on colorectal cancer

References

• Siegel RL, Miller KD, Jemal A. Cancer statistics, 2016. CA Cancer J Clin 2016; 66:7-30; PMID:26742998; https://doi.org/10.3322/caac.21332
   PubMed Web of Science ®Google Scholar
• Siegel RL, Fedewa SA, Anderson WF, Miller KD, Ma J, Rosenberg PS, Jemal A. Colorectal cancer incidence patterns in the United States, 1974–2013. J Natl Cancer Institute 2017; 109; PMID:28376186; https://doi.org/10.1093/jnci/djw322
   PubMedGoogle Scholar
• Sauer R, Fietkau R, Wittekind C, Rodel C, Martus P, Hohenberger W, Tschmelitsch J, Sabitzer H, Karstens JH, Becker H, et al. Adjuvant vs. neoadjuvant radiochemotherapy for locally advanced rectal cancer: the German trial CAO/ARO/AIO-94. Colorectal Dis 2003; 5:406-15; PMID:12925071; https://doi.org/10.1046/j.1463-1318.2003.00509.x
   PubMedGoogle Scholar
• Rodel C, Martus P, Papadoupolos T, Fuzesi L, Klimpfinger M, Fietkau R, Liersch T, Hohenberger W, Raab R, Sauer R, et al. Prognostic significance of tumor regression after preoperative chemoradiotherapy for rectal cancer. J Clin Oncol 2005; 23:8688-96; PMID:16246976; https://doi.org/10.1200/JCO.2005.02.1329
   PubMed Web of Science ®Google Scholar
• Park IJ, You YN, Agarwal A, Skibber JM, Rodriguez-Bigas MA, Eng C, Feig BW, Das P, Krishnan S, Crane CH, et al. Neoadjuvant treatment response as an early response indicator for patients with rectal cancer. J Clin Oncol 2012; 30:1770-6; PMID:22493423; https://doi.org/10.1200/JCO.2011.39.7901
   PubMed Web of Science ®Google Scholar
• Bouzourene H, Bosman FT, Seelentag W, Matter M, Coucke P. Importance of tumor regression assessment in predicting the outcome in patients with locally advanced rectal carcinoma who are treated with preoperative radiotherapy. Cancer 2002; 94:1121-30; PMID:11920483; https://doi.org/10.1002/cncr.10327
   PubMed Web of Science ®Google Scholar
• Willett CG, Duda DG, di Tomaso E, Boucher Y, Ancukiewicz M, Sahani DV, Lahdenranta J, Chung DC, Fischman AJ, Lauwers GY, et al. Efficacy, safety, and biomarkers of neoadjuvant bevacizumab, radiation therapy, and fluorouracil in rectal cancer: a multidisciplinary phase II study. J Clin Oncol 2009; 27:3020-6; PMID:19470921; https://doi.org/10.1200/JCO.2008.21.1771
   PubMed Web of Science ®Google Scholar
• Czito BG, Willett CG, Bendell JC, Morse MA, Tyler DS, Fernando NH, Mantyh CR, Blobe GC, Honeycutt W, Yu D, et al. Increased toxicity with gefitinib, capecitabine, and radiation therapy in pancreatic and rectal cancer: phase I trial results. J Clin Oncol 2006; 24:656-62; PMID:16446337; https://doi.org/10.1200/JCO.2005.04.1749
   PubMed Web of Science ®Google Scholar
• Dewdney A, Cunningham D, Tabernero J, Capdevila J, Glimelius B, Cervantes A, Tait D, Brown G, Wotherspoon A, Gonzalez de Castro D, et al. Multicenter randomized phase II clinical trial comparing neoadjuvant oxaliplatin, capecitabine, and preoperative radiotherapy with or without cetuximab followed by total mesorectal excision in patients with high-risk rectal cancer (EXPERT-C). J Clin Oncol 2012; 30:1620-7; PMID:22473163; https://doi.org/10.1200/JCO.2011.39.6036
   PubMed Web of Science ®Google Scholar
• Velenik V, Ocvirk J, Music M, Bracko M, Anderluh F, Oblak I, Edhemovic I, Brecelj E, Kropivnik M, Omejc M. Neoadjuvant capecitabine, radiotherapy, and bevacizumab (CRAB) in locally advanced rectal cancer: results of an open-label phase II study. Radiation Oncol 2011; 6:105; PMID:21880132; https://doi.org/10.1186/1748-717X-6-105
   PubMed Web of Science ®Google Scholar
• Hannun YA, Obeid LM. The Ceramide-centric universe of lipid-mediated cell regulation: stress encounters of the lipid kind. J Biol Chem 2002; 277:25847-50; PMID:12011103; https://doi.org/10.1074/jbc.R200008200
   PubMed Web of Science ®Google Scholar
• Castro BM, Prieto M, Silva LC. Ceramide: a simple sphingolipid with unique biophysical properties. Prog Lipid Res 2014; 54:53-67; PMID:24513486; https://doi.org/10.1016/j.plipres.2014.01.004
   PubMed Web of Science ®Google Scholar
• Ogretmen B. Sphingolipids in cancer: regulation of pathogenesis and therapy. FEBS Lett 2006; 580:5467-76; PMID:16970943; https://doi.org/10.1016/j.febslet.2006.08.052
   PubMed Web of Science ®Google Scholar
• Ogretmen B, Hannun YA. Biologically active sphingolipids in cancer pathogenesis and treatment. Nat Rev Cancer 2004; 4:604-16; PMID:15286740; https://doi.org/10.1038/nrc1411
   PubMed Web of Science ®Google Scholar
• Mullen TD, Hannun YA, Obeid LM. Ceramide synthases at the centre of sphingolipid metabolism and biology. Biochem J 2012; 441:789-802; PMID:22248339; https://doi.org/10.1042/BJ20111626
   PubMed Web of Science ®Google Scholar
• Ebel P, Imgrund S, Vom Dorp K, Hofmann K, Maier H, Drake H, Degen J, Dörmann P, Eckhardt M, Franz T, et al. Ceramide synthase 4 deficiency in mice causes lipid alterations in sebum and results in alopecia. Biochem J 2014; 461:147-58; PMID:24738593; https://doi.org/10.1042/BJ20131242
   PubMed Web of Science ®Google Scholar
• Jennemann R, Rabionet M, Gorgas K, Epstein S, Dalpke A, Rothermel U, Bayerle A, van der Hoeven F, Imgrund S, Kirsch J, et al. Loss of ceramide synthase 3 causes lethal skin barrier disruption. Hum Mol Genet 2012; 21:586-608; PMID:22038835; https://doi.org/10.1093/hmg/ddr494
   PubMed Web of Science ®Google Scholar
• Grosch S, Schiffmann S, Geisslinger G. Chain length-specific properties of ceramides. Prog Lipid Res 2012; 51:50-62; PMID:22133871; https://doi.org/10.1016/j.plipres.2011.11.001
   PubMed Web of Science ®Google Scholar
• Pewzner-Jung Y, Brenner O, Braun S, Laviad EL, Ben-Dor S, Feldmesser E, Horn-Saban S, Amann-Zalcenstein D, Raanan C, Berkutzki T, et al. A critical role for ceramide synthase 2 in liver homeostasis: II. insights into molecular changes leading to hepatopathy. J Biol Chem 2010; 285:10911-23; PMID:20110366; https://doi.org/10.1074/jbc.M109.077610
   PubMed Web of Science ®Google Scholar
• Pewzner-Jung Y, Park H, Laviad EL, Silva LC, Lahiri S, Stiban J, Erez-Roman R, Brügger B, Sachsenheimer T, Wieland F, et al. A critical role for ceramide synthase 2 in liver homeostasis: I. alterations in lipid metabolic pathways. J Biol Chem 2010; 285:10902-10; PMID:20110363; https://doi.org/10.1074/jbc.M109.077594
   PubMed Web of Science ®Google Scholar
• Wegner MS, Schiffmann S, Parnham MJ, Geisslinger G, Grosch S. The enigma of ceramide synthase regulation in mammalian cells. Prog Lipid Res 2016; 63:93-119; PMID:27180613; https://doi.org/10.1016/j.plipres.2016.03.006
   PubMed Web of Science ®Google Scholar
• Levy M, Futerman AH. Mammalian ceramide synthases. IUBMB Life 2010; 62:347-56; PMID:20222015; https://doi.org/10.1002/iub.319
   PubMed Web of Science ®Google Scholar
• Neubauer HA, Pitson SM. Roles, regulation and inhibitors of sphingosine kinase 2. FEBS J 2013; 280:5317-36; PMID:23638983; https://doi.org/10.1111/febs.12314
   PubMed Web of Science ®Google Scholar
• Vesper H, Schmelz EM, Nikolova-Karakashian MN, Dillehay DL, Lynch DV, Merrill AH Jr. Sphingolipids in food and the emerging importance of sphingolipids to nutrition. J Nutrition 1999; 129:1239-50; PMID:10395583
   PubMed Web of Science ®Google Scholar
• Markowitz SD, Bertagnolli MM. Molecular origins of cancer: Molecular basis of colorectal cancer. N Eng J Med 2009; 361:2449-60; PMID:20018966; https://doi.org/10.1056/NEJMra0804588
   PubMed Web of Science ®Google Scholar
• Kumar A, Pandurangan AK, Lu F, Fyrst H, Zhang M, Byun HS, Bittman R, Saba JD. Chemopreventive sphingadienes downregulate Wnt signaling via a PP2A/Akt/GSK3beta pathway in colon cancer. Carcinogenesis 2012; 33:1726-35; PMID:22581840; https://doi.org/10.1093/carcin/bgs174
   PubMed Web of Science ®Google Scholar
• Symolon H, Schmelz EM, Dillehay DL, Merrill AH Jr. Dietary soy sphingolipids suppress tumorigenesis and gene expression in 1,2-dimethylhydrazine-treated CF1 mice and ApcMin/+ mice. J Nutrition 2004; 134:1157-61; PMID:15113963
   PubMed Web of Science ®Google Scholar
• Schmelz EM, Merrill AH, Jr. Ceramides and ceramide metabolites in cell regulation: evidence for dietary sphingolipids as inhibitors of colon carcinogenesis. Nutrition 1998; 14:717-9; PMID:9760598
   PubMed Web of Science ®Google Scholar
• Schmelz EM, Roberts PC, Kustin EM, Lemonnier LA, Sullards MC, Dillehay DL, Merrill AH Jr. Modulation of intracellular beta-catenin localization and intestinal tumorigenesis in vivo and in vitro by sphingolipids. Cancer Res 2001; 61:6723-9; PMID:11559543
   PubMed Web of Science ®Google Scholar
• Berra B, Colombo I, Sottocornola E, Giacosa A. Dietary sphingolipids in colorectal cancer prevention. Euro J Cancer Prev 2002; 11:193-7; PMID:11984139; https://doi.org/10.1097/00008469-200204000-00013
   PubMed Web of Science ®Google Scholar
• Schmelz EM, Crall KJ, Larocque R, Dillehay DL, Merrill AH Jr. Uptake and metabolism of sphingolipids in isolated intestinal loops of mice. J Nutrition 1994; 124:702-12; PMID:8169662
   PubMed Web of Science ®Google Scholar
• Wu J, Liu F, Nilsson A, Duan RD. Pancreatic trypsin cleaves intestinal alkaline sphingomyelinase from mucosa and enhances the sphingomyelinase activity. Am J Physiol Gastrointest Liver Physiol 2004; 287:G967-73; PMID:15205117; https://doi.org/10.1152/ajpgi.00190.2004
   PubMed Web of Science ®Google Scholar
• Zhang P, Li B, Gao S, Duan RD. Dietary sphingomyelin inhibits colonic tumorigenesis with an up-regulation of alkaline sphingomyelinase expression in ICR mice. Anticancer Res 2008; 28:3631-5; PMID:19189644
   PubMed Web of Science ®Google Scholar
• Baxter NT, Zackular JP, Chen GY, Schloss PD. Structure of the gut microbiome following colonization with human feces determines colonic tumor burden. Microbiome 2014; 2:20; PMID:24967088; https://doi.org/10.1186/2049-2618-2-20
   PubMed Web of Science ®Google Scholar
• Weir TL, Manter DK, Sheflin AM, Barnett BA, Heuberger AL, Ryan EP. Stool microbiome and metabolome differences between colorectal cancer patients and healthy adults. PloS One 2013; 8:e70803; PMID:23940645; https://doi.org/10.1371/journal.pone.0070803
   PubMed Web of Science ®Google Scholar
• Eckburg PB, Bik EM, Bernstein CN, Purdom E, Dethlefsen L, Sargent M, Gill SR, Nelson KE, Relman DA. Diversity of the human intestinal microbial flora. Science 2005; 308:1635-8; PMID:15831718; https://doi.org/10.1126/science.1110591
   PubMed Web of Science ®Google Scholar
• Olsen I, Jantzen E. Sphingolipids in Bacteria and Fungi. Anaerobe 2001; 7:103-12; https://doi.org/10.1006/anae.2001.0376
   Web of Science ®Google Scholar
• An D, Na C, Bielawski J, Hannun YA, Kasper DL. Membrane sphingolipids as essential molecular signals for Bacteroides survival in the intestine. Proc Natl Acad Sci U S A 2011; 108(Suppl 1):4666-71; PMID:20855611; https://doi.org/10.1073/pnas.1001501107
   PubMed Web of Science ®Google Scholar
• An D, Oh SF, Olszak T, Neves JF, Avci FY, Erturk-Hasdemir D, Lu X, Zeissig S, Blumberg RS, Kasper DL. Sphingolipids from a symbiotic microbe regulate homeostasis of host intestinal natural killer T cells. Cell 2014; 156:123-33; PMID:24439373; https://doi.org/10.1016/j.cell.2013.11.042
   PubMed Web of Science ®Google Scholar
• Boleij A, Hechenbleikner EM, Goodwin AC, Badani R, Stein EM, Lazarev MG, Ellis B, Carroll KC, Albesiano E, Wick EC, et al. The Bacteroides fragilis toxin gene is prevalent in the colon mucosa of colorectal cancer patients. Clin Infect Dis 2015; 60:208-15; PMID:25305284; https://doi.org/10.1093/cid/ciu787
   PubMed Web of Science ®Google Scholar
• Toprak NU, Yagci A, Gulluoglu BM, Akin ML, Demirkalem P, Celenk T, Soyletir G. A possible role of Bacteroides fragilis enterotoxin in the aetiology of colorectal cancer. Clin Microbiol Infect 2006; 12:782-6; PMID:16842574; https://doi.org/10.1111/j.1469-0691.2006.01494.x
   PubMed Web of Science ®Google Scholar
• Deng Z, Mu J, Tseng M, Wattenberg B, Zhuang X, Egilmez NK, Wang Q, Zhang L, Norris J, Guo H, et al. Enterobacteria-secreted particles induce production of exosome-like S1P-containing particles by intestinal epithelium to drive Th17-mediated tumorigenesis. Nat Commun 2015; 6:6956; PMID:25907800; https://doi.org/10.1038/ncomms7956
   PubMed Web of Science ®Google Scholar
• Bernstein CN, Blanchard JF, Kliewer E, Wajda A. Cancer risk in patients with inflammatory bowel disease: a population-based study. Cancer 2001; 91:854-62; PMID:11241255; https://doi.org/10.1002/1097-0142(20010215)91:4%3c854::AID-CNCR1073%3e3.0.CO;2-Z
   PubMed Web of Science ®Google Scholar
• Angulo S, Morales A, Danese S, Llacuna L, Masamunt MC, Pultz N, Cifone MG, De Simone C, Delgado S, Vila J, et al. Probiotic sonicates selectively induce mucosal immune cells apoptosis through ceramide generation via neutral sphingomyelinase. PloS One 2011; 6:e16953; PMID:21408067; https://doi.org/10.1371/journal.pone.0016953
   PubMed Web of Science ®Google Scholar
• Kekkonen RA, Sysi-Aho M, Seppanen-Laakso T, Julkunen I, Vapaatalo H, Oresic M, Korpela R. Effect of probiotic Lactobacillus rhamnosus GG intervention on global serum lipidomic profiles in healthy adults. World J Gastroenterol 2008; 14:3188-94; PMID:18506924; https://doi.org/10.3748/wjg.14.3188
   PubMed Web of Science ®Google Scholar
• Park JW, Park WJ, Futerman AH. Ceramide synthases as potential targets for therapeutic intervention in human diseases. Biochim Biophys Acta 2014; 1841:671-81; PMID:24021978; https://doi.org/10.1016/j.bbalip.2013.08.019
   PubMed Web of Science ®Google Scholar
• Derer S, Till A, Haesler R, Sina C, Grabe N, Jung S, Nikolaus S, Kuehbacher T, Groetzinger J, Rose-John S, et al. mTNF reverse signalling induced by TNFalpha antagonists involves a GDF-1 dependent pathway: implications for Crohn's disease. Gut 2013; 62:376-86; PMID:22535372; https://doi.org/10.1136/gutjnl-2011-300384
   PubMed Web of Science ®Google Scholar
• Mizutani Y, Mitsutake S, Tsuji K, Kihara A, Igarashi Y. Ceramide biosynthesis in keratinocyte and its role in skin function. Biochimie 2009; 91:784-90; PMID:19364519; https://doi.org/10.1016/j.biochi.2009.04.001
   PubMed Web of Science ®Google Scholar
• Laviad EL, Albee L, Pankova-Kholmyansky I, Epstein S, Park H, Merrill AH Jr, Futerman AH. Characterization of ceramide synthase 2: tissue distribution, substrate specificity, and inhibition by sphingosine 1-phosphate. J Biol Chem 2008; 283:5677-84; PMID:18165233; https://doi.org/10.1074/jbc.M707386200
   PubMed Web of Science ®Google Scholar
• Fekry B, Esmaeilniakooshkghazi A, Krupenko SA, Krupenko NI. Ceramide Synthase 6 Is a Novel Target of Methotrexate Mediating Its Antiproliferative Effect in a p53-Dependent Manner. PloS One 2016; 11:e0146618; PMID:26783755; https://doi.org/10.1371/journal.pone.0146618
   PubMed Web of Science ®Google Scholar
• Riebeling C, Allegood JC, Wang E, Merrill AH Jr, Futerman AH. Two mammalian longevity assurance gene (LAG1) family members, trh1 and trh4, regulate dihydroceramide synthesis using different fatty acyl-CoA donors. J Biol Chem 2003; 278:43452-9; PMID:12912983; https://doi.org/10.1074/jbc.M307104200
   PubMed Web of Science ®Google Scholar
• Ebel P, Vom Dorp K, Petrasch-Parwez E, Zlomuzica A, Kinugawa K, Mariani J, Minich D, Ginkel C, Welcker J, Degen J, et al. Inactivation of ceramide synthase 6 in mice results in an altered sphingolipid metabolism and behavioral abnormalities. J Biol Chem 2013; 288:21433-47; PMID:23760501; https://doi.org/10.1074/jbc.M113.479907
   PubMed Web of Science ®Google Scholar
• Edmond V, Dufour F, Poiroux G, Shoji K, Malleter M, Fouque A, Tauzin S, Rimokh R, Sergent O, Penna A, et al. Downregulation of ceramide synthase-6 during epithelial-to-mesenchymal transition reduces plasma membrane fluidity and cancer cell motility. Oncogene 2015; 34:996-1005; PMID:24632610; https://doi.org/10.1038/onc.2014.55
   PubMed Web of Science ®Google Scholar
• Hertervig E, Nilsson A, Nyberg L, Duan RD. Alkaline sphingomyelinase activity is decreased in human colorectal carcinoma. Cancer 1997; 79:448-53; PMID:9028353
   PubMed Web of Science ®Google Scholar
• Wang K, Xu R, Snider AJ, Schrandt J, Li Y, Bialkowska AB, Li M, Zhou J, Hannun YA, Obeid LM, et al. Alkaline ceramidase 3 deficiency aggravates colitis and colitis-associated tumorigenesis in mice by hyperactivating the innate immune system. Cell Death Dis 2016; 7:e2124; PMID:26938296; https://doi.org/10.1038/cddis.2016.36
   PubMed Web of Science ®Google Scholar
• Koch J, Gartner S, Li CM, Quintern LE, Bernardo K, Levran O, Schnabel D, Desnick RJ, Schuchman EH, Sandhoff K, et al. Molecular cloning and characterization of a full-length complementary DNA encoding human acid ceramidase. Identification Of the first molecular lesion causing Farber disease. J Biol Chem 1996; 271:33110-5; PMID:8955159; https://doi.org/10.1074/jbc.271.51.33110
   PubMed Web of Science ®Google Scholar
• Park JH, Schuchman EH. Acid ceramidase and human disease. Biochim Biophys Acta 2006; 1758:2133-8; PMID:17064658; https://doi.org/10.1016/j.bbamem.2006.08.019
   PubMed Web of Science ®Google Scholar
• Eliyahu E, Park JH, Shtraizent N, He X, Schuchman EH. Acid ceramidase is a novel factor required for early embryo survival. FASEB J 2007; 21:1403-9; PMID:17264167; https://doi.org/10.1096/fj.06-7016com
   PubMed Web of Science ®Google Scholar
• Seelan RS, Qian C, Yokomizo A, Bostwick DG, Smith DI, Liu W. Human acid ceramidase is overexpressed but not mutated in prostate cancer. Genes Chromosomes Cancer 2000; 29:137-46; PMID:10959093; https://doi.org/10.1002/1098-2264(2000)9999:9999%3c::AID-GCC1018%3e3.0.CO;2-E
   PubMed Web of Science ®Google Scholar
• Tirodkar TS, Lu P, Bai A, Scheffel MJ, Gencer S, Garrett-Mayer E, Bielawska A, Ogretmen B, Voelkel-Johnson C, et al. Expression of Ceramide Synthase 6 Transcriptionally Activates Acid Ceramidase in a c-Jun N-terminal Kinase (JNK)-dependent Manner. J Biol Chem 2015; 290:13157-67; PMID:25839235; https://doi.org/10.1074/jbc.M114.631325
   PubMed Web of Science ®Google Scholar
• Cheng JC, Bai A, Beckham TH, Marrison ST, Yount CL, Young K, Lu P, Bartlett AM, Wu BX, Keane BJ, et al. Radiation-induced acid ceramidase confers prostate cancer resistance and tumor relapse. J Clin Invest 2013; 123:4344-58; PMID:24091326; https://doi.org/10.1172/JCI64791
   PubMed Web of Science ®Google Scholar
• Kono M, Dreier JL, Ellis JM, Allende ML, Kalkofen DN, Sanders KM, Bielawski J, Bielawska A, Hannun YA, Proia RL. Neutral ceramidase encoded by the Asah2 gene is essential for the intestinal degradation of sphingolipids. J Biol Chem 2006; 281:7324-31; PMID:16380386; https://doi.org/10.1074/jbc.M508382200
   PubMed Web of Science ®Google Scholar
• Garcia-Barros M, Coant N, Kawamori T, Wada M, Snider AJ, Truman JP, Wu BX, Furuya H, Clarke CJ, Bialkowska AB, et al. Role of neutral ceramidase in colon cancer. FASEB J 2016; 30:4159-71; PMID:27609772; https://doi.org/10.1096/fj.201600611R
   PubMed Web of Science ®Google Scholar
• Kawamori T, Kaneshiro T, Okumura M, Maalouf S, Uflacker A, Bielawski J, Hannun YA, Obeid LM. Role for sphingosine kinase 1 in colon carcinogenesis. FASEB J 2009; 23:405-14; PMID:18824518; https://doi.org/10.1096/fj.08-117572
   PubMed Web of Science ®Google Scholar
• Long J, Xie Y, Yin J, Lu W, Fang S. SphK1 promotes tumor cell migration and invasion in colorectal cancer. Tumour Biol 2016; 37:6831-6; PMID:26662312; https://doi.org/10.1007/s13277-015-4542-4
   PubMed Web of Science ®Google Scholar
• Liang J, Nagahashi M, Kim EY, Harikumar KB, Yamada A, Huang WC, Hait NC, Allegood JC, Price MM, Avni D, et al. Sphingosine-1-phosphate links persistent STAT3 activation, chronic intestinal inflammation, and development of colitis-associated cancer. Cancer Cell 2013; 23:107-20; PMID:23273921; https://doi.org/10.1016/j.ccr.2012.11.013
   PubMed Web of Science ®Google Scholar
• Zhang L, Liu X, Zuo Z, Hao C, Ma Y. Sphingosine kinase 2 promotes colorectal cancer cell proliferation and invasion by enhancing MYC expression. Tumour Biol 2016; 37:8455-60; PMID:26733171; https://doi.org/10.1007/s13277-015-4700-8
   PubMed Web of Science ®Google Scholar
• Mizutani N, Omori Y, Tanaka K, Ito H, Takagi A, Kojima T, Nakatochi M, Ogiso H, Kawamoto Y, Nakamura M, et al. Increased SPHK2 transcription of human colon cancer cells in serum-depleted culture: The involvement of CREB transcription factor. J Cell Biochem 2015; 116:2227-38; PMID:25808826; https://doi.org/10.1002/jcb.25173
   PubMed Web of Science ®Google Scholar
• Schrecengost RS, Keller SN, Schiewer MJ, Knudsen KE, Smith CD. Downregulation of critical oncogenes by the selective SK2 inhibitor ABC294640 hinders prostate cancer progression. Mol Cancer Res 2015; 13:1591-601; PMID:26271487; https://doi.org/10.1158/1541-7786.MCR-14-0626
   PubMed Web of Science ®Google Scholar
• He TC, Sparks AB, Rago C, Hermeking H, Zawel L, da Costa LT, Morin PJ, Vogelstein B, Kinzler KW. Identification of c-MYC as a target of the APC pathway. Science 1998; 281:1509-12; PMID:9727977; https://doi.org/10.1126/science.281.5382.1509
   PubMed Web of Science ®Google Scholar
• Siskind LJ, Kolesnick RN, Colombini M. Ceramide channels increase the permeability of the mitochondrial outer membrane to small proteins. J Biol Chem 2002; 277:26796-803; PMID:12006562; https://doi.org/10.1074/jbc.M200754200
   PubMed Web of Science ®Google Scholar
• Santana P, Pena LA, Haimovitz-Friedman A, Martin S, Green D, McLoughlin M, Cordon-Cardo C, Schuchman EH, Fuks Z, Kolesnick R. Acid sphingomyelinase-deficient human lymphoblasts and mice are defective in radiation-induced apoptosis. Cell 1996; 86:189-99; PMID:8706124; https://doi.org/10.1016/S0092-8674(00)80091-4
   PubMed Web of Science ®Google Scholar
• Paris F, Fuks Z, Kang A, Capodieci P, Juan G, Ehleiter D, Haimovitz-Friedman A, Cordon-Cardo C, Kolesnick R. Endothelial apoptosis as the primary lesion initiating intestinal radiation damage in mice. Science 2001; 293:293-7; PMID:11452123; https://doi.org/10.1126/science.1060191
   PubMed Web of Science ®Google Scholar
• Deng X, Yin X, Allan R, Lu DD, Maurer CW, Haimovitz-Friedman A, Fuks Z, Shaham S, Kolesnick R. Ceramide biogenesis is required for radiation-induced apoptosis in the germ line of C. elegans. Science 2008; 322:110-5; PMID:18832646; https://doi.org/10.1126/science.1158111
   PubMed Web of Science ®Google Scholar
• Kolesnick R, Fuks Z. Radiation and ceramide-induced apoptosis. Oncogene 2003; 22:5897-906; PMID:12947396; https://doi.org/10.1038/sj.onc.1206702
   PubMed Web of Science ®Google Scholar
• Mesicek J, Lee H, Feldman T, Jiang X, Skobeleva A, Berdyshev EV, Haimovitz-Friedman A, Fuks Z, Kolesnick R. Ceramide synthases 2, 5, and 6 confer distinct roles in radiation-induced apoptosis in HeLa cells. Cell Signal 2010; 22:1300-7; PMID:20406683; https://doi.org/10.1016/j.cellsig.2010.04.006
   PubMed Web of Science ®Google Scholar
• Yacoub A, Hamed HA, Allegood J, Mitchell C, Spiegel S, Lesniak MS, Ogretmen B, Dash R, Sarkar D, Broaddus WC, et al. PERK-dependent regulation of ceramide synthase 6 and thioredoxin play a key role in mda-7/IL-24-induced killing of primary human glioblastoma multiforme cells. Cancer Res 2010; 70:1120-9; PMID:20103619; https://doi.org/10.1158/0008-5472.CAN-09-4043
   PubMed Web of Science ®Google Scholar
• Walker T, Mitchell C, Park MA, Yacoub A, Rahmani M, Haussinger D, Reinehr R, Voelkel-Johnson C, Fisher PB, Grant S, et al. 17-allylamino-17-demethoxygeldanamycin and MEK1/2 inhibitors kill GI tumor cells via Ca2+-dependent suppression of GRP78/BiP and induction of ceramide and reactive oxygen species. Mol Cancer Ther 2010; 9:1378-95; PMID:20442308; https://doi.org/10.1158/1535-7163.MCT-09-1131
   PubMed Web of Science ®Google Scholar
• Separovic D, Breen P, Joseph N, Bielawski J, Pierce JS, VAN Buren E, Gudz TI. Ceramide synthase 6 knockdown suppresses apoptosis after photodynamic therapy in human head and neck squamous carcinoma cells. Anticancer Res 2012; 32:753-60; PMID:22399588
   PubMed Web of Science ®Google Scholar
• White-Gilbertson S, Mullen T, Senkal C, Lu P, Ogretmen B, Obeid L, Voelkel-Johnson C. Ceramide synthase 6 modulates TRAIL sensitivity and nuclear translocation of active caspase-3 in colon cancer cells. Oncogene 2009; 28:1132-41; PMID:19137010; https://doi.org/10.1038/onc.2008.468
   PubMed Web of Science ®Google Scholar
• Walker T, Mitchell C, Park MA, Yacoub A, Graf M, Rahmani M, Houghton PJ, Voelkel-Johnson C, Grant S, Dent P. Sorafenib and vorinostat kill colon cancer cells by CD95-dependent and -independent mechanisms. Mol Pharmacol 2009; 76:342-55; PMID:19483104; https://doi.org/10.1124/mol.109.056523
   PubMed Web of Science ®Google Scholar
• Park MA, Walker T, Martin AP, Allegood J, Vozhilla N, Emdad L, Sarkar D, Rahmani M, Graf M, Yacoub A, et al. MDA-7/IL-24-induced cell killing in malignant renal carcinoma cells occurs by a ceramide/CD95/PERK-dependent mechanism. Mol Cancer Ther 2009; 8:1280-91; PMID:19417161; https://doi.org/10.1158/1535-7163.MCT-09-0073
   PubMed Web of Science ®Google Scholar
• Park MA, Mitchell C, Zhang G, Yacoub A, Allegood J, Haussinger D, Reinehr R, Larner A, Spiegel S, Fisher PB, et al. Vorinostat and sorafenib increase CD95 activation in gastrointestinal tumor cells through a Ca(2+)-de novo ceramide-PP2A-reactive oxygen species-dependent signaling pathway. Cancer Res 2010; 70:6313-24; PMID:20631069; https://doi.org/10.1158/0008-5472.CAN-10-0999
   PubMed Web of Science ®Google Scholar
• Park MA, Reinehr R, Haussinger D, Voelkel-Johnson C, Ogretmen B, Yacoub A, Grant S, Dent P. Sorafenib activates CD95 and promotes autophagy and cell death via Src family kinases in gastrointestinal tumor cells. Mol Cancer Ther 2010; 9:2220-31; PMID:20682655; https://doi.org/10.1158/1535-7163.MCT-10-0274
   PubMed Web of Science ®Google Scholar
• Coant N, Sakamoto W, Mao C, Hannun YA. Ceramidases, roles in sphingolipid metabolism and in health and disease. Adv Biol Regulation 2017; 63:122-31; PMID:27771292; https://doi.org/10.1016/j.jbior.2016.10.002
   PubMedGoogle Scholar
• Bedia C, Casas J, Andrieu-Abadie N, Fabrias G, Levade T. Acid ceramidase expression modulates the sensitivity of A375 melanoma cells to dacarbazine. J Biol Chem 2011; 286:28200-9; PMID:21700700; https://doi.org/10.1074/jbc.M110.216382
   PubMed Web of Science ®Google Scholar
• Tan SF, Liu X, Fox TE, Barth BM, Sharma A, Turner SD, Awwad A, Dewey A, Doi K, Spitzer B, et al. Acid ceramidase is upregulated in AML and represents a novel therapeutic target. Oncotarget 2016; 7:83208-22; PMID:27825124
   PubMed Web of Science ®Google Scholar
• Sanger N, Ruckhaberle E, Gyorffy B, Engels K, Heinrich T, Fehm T, Graf A, Holtrich U, Becker S, Karn T. Acid ceramidase is associated with an improved prognosis in both DCIS and invasive breast cancer. Mol Oncol 2014; 9(1):58-67; PMID:25131496; https://doi.org/10.1016/j.molonc.2014.07.016
   PubMed Web of Science ®Google Scholar
• Hanker LC, Karn T, Holtrich U, Gatje R, Rody A, Heinrich T, Ruckhäberle E, Engels K. Acid ceramidase (AC)–a key enzyme of sphingolipid metabolism–correlates with better prognosis in epithelial ovarian cancer. Int J Gynecol Pathol 2013; 32:249-57; PMID:23518908; https://doi.org/10.1097/PGP.0b013e3182673982
   PubMed Web of Science ®Google Scholar
• Sabbadini RA. Sphingosine-1-phosphate antibodies as potential agents in the treatment of cancer and age-related macular degeneration. Br J Pharmacol 2011; 162:1225-38; PMID:21091645; https://doi.org/10.1111/j.1476-5381.2010.01118.x
   PubMed Web of Science ®Google Scholar
• Pitman MR, Costabile M, Pitson SM. Recent advances in the development of sphingosine kinase inhibitors. Cell Signal 2016; 28:1349-63; PMID:27297359; https://doi.org/10.1016/j.cellsig.2016.06.007
   PubMed Web of Science ®Google Scholar
• Saied EM, Arenz C. Small molecule inhibitors of ceramidases. Cell Physiol Biochem 2014; 34:197-212; PMID:24977492; https://doi.org/10.1159/000362995
   PubMed Web of Science ®Google Scholar
• Szulc ZM, Bielawski J, Gracz H, Gustilo M, Mayroo N, Hannun YA, Obeid LM, Bielawska A. Tailoring structure-function and targeting properties of ceramides by site-specific cationization. Bioorg Med Chem 2006; 14:7083-104; PMID:16919460; https://doi.org/10.1016/j.bmc.2006.07.016
   PubMed Web of Science ®Google Scholar
• Zhang L, Wang X, Bullock AJ, Callea M, Shah H, Song J, Moreno K, Visentin B, Deutschman D, Alsop DC, et al. Anti-S1P Antibody as a Novel Therapeutic Strategy for VEGFR TKI-Resistant Renal Cancer. Clin Cancer Res 2015; 21:1925-34; PMID:25589614; https://doi.org/10.1158/1078-0432.CCR-14-2031
   PubMed Web of Science ®Google Scholar
• Bai A, Szulc ZM, Bielawski J, Pierce JS, Rembiesa B, Terzieva S, Mao C, Xu R, Wu B, Clarke CJ, et al. Targeting (cellular) lysosomal acid ceramidase by B13: design, synthesis and evaluation of novel DMG-B13 ester prodrugs. Bioorg Med Chem 2014; 22:6933-44; PMID:25456083; https://doi.org/10.1016/j.bmc.2014.10.025
   PubMed Web of Science ®Google Scholar
• Korbelik M, Banath J, Zhang W, Saw KM, Szulc ZM, Bielawska A, Separovic D. Interaction of acid ceramidase inhibitor LCL521 with tumor response to photodynamic therapy and photodynamic therapy-generated vaccine. Int J Cancer 2016; 139:1372-8; PMID:27136745; https://doi.org/10.1002/ijc.30171
   PubMed Web of Science ®Google Scholar
• French KJ, Zhuang Y, Maines LW, Gao P, Wang W, Beljanski V, Upson JJ, Green CL, Keller SN, Smith CD. Pharmacology and antitumor activity of ABC294640, a selective inhibitor of sphingosine kinase-2. J Pharmacol Exp Ther 2010; 333:129-39; PMID:20061445; https://doi.org/10.1124/jpet.109.163444
   PubMed Web of Science ®Google Scholar
• Ju T, Gao D, Fang ZY. Targeting colorectal cancer cells by a novel sphingosine kinase 1 inhibitor PF-543. Biochem Biophys Res Commun 2016; 470:728-34; PMID:26775841; https://doi.org/10.1016/j.bbrc.2016.01.053
   PubMed Web of Science ®Google Scholar
• Sharma AK. Sphingo-guanidines and their use as inhibitors of sphingosine kinase (WO2010078247). Expert Opin Ther Pat 2011; 21:807-12; PMID:21457086; https://doi.org/10.1517/13543776.2011.573787
   PubMed Web of Science ®Google Scholar
• Chumanevich AA, Poudyal D, Cui X, Davis T, Wood PA, Smith CD, Hofseth LJ. Suppression of colitis-driven colon cancer in mice by a novel small molecule inhibitor of sphingosine kinase. Carcinogenesis 2010; 31:1787-93; PMID:20688834; https://doi.org/10.1093/carcin/bgq158
   PubMed Web of Science ®Google Scholar
• Xun C, Chen MB, Qi L, Tie-Ning Z, Peng X, Ning L, Zhi-Xiao C, Li-Wei W. Targeting sphingosine kinase 2 (SphK2) by ABC294640 inhibits colorectal cancer cell growth in vitro and in vivo. J Exp Clin Cancer Res 2015; 34:94; https://doi.org/10.1186/s13046-015-0205-y
   PubMed Web of Science ®Google Scholar
• Britten CD, Thomas MB, Garrett-Mayer E, Chin SH, Shirai K, Ogretmen B, Bentz TA, Brisendine A, Anderton K, Cusack SL, et al. A phase I study of ABC294640, A First-in-Class sphingosine kinase-2 inhibitor, in patients with advanced solid tumors. Clin Cancer Res 2017; PMID:28420720; https://doi.org/10.1158/1078-0432.CCR-16-2363
   PubMed Web of Science ®Google Scholar
• Lewis CS, Voelkel-Johnson C, Smith CD. Suppression of c-Myc and RRM2 expression in pancreatic cancer cells by the sphingosine kinase-2 inhibitor ABC294640. Oncotarget 2016; 7:60181-92; PMID:27517489
   PubMed Web of Science ®Google Scholar
• Venant H, Rahmaniyan M, Jones EE, Lu P, Lilly MB, Garrett-Mayer E, Drake RR, Kraveka JM, Smith CD, Voelkel-Johnson C. The sphingosine kinase 2 inhibitor ABC294640 reduces the growth of prostate cancer cells and results in accumulation of dihydroceramides in vitro and in vivo. Mol Cancer Ther 2015; 14:2744-52; PMID:26494858; https://doi.org/10.1158/1535-7163.MCT-15-0279
   PubMed Web of Science ®Google Scholar
• Venkata JK, An N, Stuart R, Costa LJ, Cai H, Coker W, Song JH, Gibbs K, Matson T, Garrett-Mayer E, et al. Inhibition of sphingosine kinase 2 downregulates the expression of c-Myc and Mcl-1 and induces apoptosis in multiple myeloma. Blood 2014; 124:1915-25; PMID:25122609; https://doi.org/10.1182/blood-2014-03-559385
   PubMed Web of Science ®Google Scholar
• Hou Q, Jin J, Zhou H, Novgorodov SA, Bielawska A, Szulc ZM, Hannun YA, Obeid LM, Hsu YT. Mitochondrially targeted ceramides preferentially promote autophagy, retard cell growth, and induce apoptosis. J Lipid Res 2011; 52:278-88; PMID:21081756; https://doi.org/10.1194/jlr.M012161
   PubMed Web of Science ®Google Scholar
• Sentelle RD, Senkal CE, Jiang W, Ponnusamy S, Gencer S, Selvam SP, Ramshesh VK, Peterson YK, Lemasters JJ, Szulc ZM, et al. Ceramide targets autophagosomes to mitochondria and induces lethal mitophagy. Nat Chem Biol 2012; 8:831-8; PMID:22922758; https://doi.org/10.1038/nchembio.1059
   PubMed Web of Science ®Google Scholar
• Dahm F, Bielawska A, Nocito A, Georgiev P, Szulc ZM, Bielawski J, Jochum W, Dindo D, Hannun YA, Clavien PA. Mitochondrially targeted ceramide LCL-30 inhibits colorectal cancer in mice. Br J Cancer 2008; 98:98-105; PMID:18026195; https://doi.org/10.1038/sj.bjc.6604099
   PubMed Web of Science ®Google Scholar
• Dindo D, Dahm F, Szulc Z, Bielawska A, Obeid LM, Hannun YA, Graf R, Clavien PA. Cationic long-chain ceramide LCL-30 induces cell death by mitochondrial targeting in SW403 cells. Mol Cancer Ther 2006; 5:1520-9; PMID:16818511; https://doi.org/10.1158/1535-7163.MCT-05-0513
   PubMed Web of Science ®Google Scholar
• Barth BM, Cabot MC, Kester M. Ceramide-based therapeutics for the treatment of cancer. Anticancer Agents Med Chem 2011; 11:911-9; PMID:21707481; https://doi.org/10.2174/187152011797655177
   PubMed Web of Science ®Google Scholar
• Hankins JL, Doshi UA, Haakenson JK, Young MM, Barth BM, Kester M. The therapeutic potential of nanoscale sphingolipid technologies. Handbook Exp Pharmacol 2013:197-210; PMID:23579457; https://doi.org/10.1007/978-3-7091-1368-4_11
   PubMedGoogle Scholar
• Kester M, Bassler J, Fox TE, Carter CJ, Davidson JA, Parette MR. Preclinical development of a C6-ceramide NanoLiposome, a novel sphingolipid therapeutic. Biol Chem 2015; 396:737-47; PMID:25838296; https://doi.org/10.1515/hsz-2015-0129
   PubMed Web of Science ®Google Scholar
• Lin L, Liu A, Peng Z, Lin HJ, Li PK, Li C, Lin J. STAT3 is necessary for proliferation and survival in colon cancer-initiating cells. Cancer Res 2011; 71:7226-37; PMID:21900397; https://doi.org/10.1158/0008-5472.CAN-10-4660
   PubMed Web of Science ®Google Scholar