Abstract
Colorectal cancer (CRC) is one of the most commonly diagnosed cancers and causes of cancer death in developed countries. SphK2 is overexpressed in a number of aggressive human carcinomas; however, the expression profile and potential function of SphK2 in CRC are still unknown. In this study, we investigated the SphK2 expression in tumoral tissue and the matched normal mucosae using quantitative real-time PCR (qRT-PCR), Western blot, and immunohistochemistry. We also evaluated the impact of SphK2 knockdown on CRC cell proliferation and metastasis in vitro. SphK2 was significantly upregulated in CRC tissue as compared to the matched normal mucosae, and significant overexpression was found in the LoVo CRC cell line. SphK2 depletion by specific small interfering RNA (siRNA) in the CRC cell line was found to affect cell proliferation and cell migration. Our data suggest that the pathogenesis of CRC maybe mediated by SphK2, and SphK2 could represent a selective target for the molecularly targeted treatments of CRC.
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Noura S, Ohue M, Shingai T, Kano S, Ohigashi H, Yano M, et al. Effects of intraperitoneal chemotherapy with mitomycin C on the prevention of peritoneal recurrence in colorectal cancer patients with positive peritoneal lavage cytology findings. Ann Surg Oncol. 2011;18:396–404.
Zhao L, Liu Y, Sun X, Peng K, Ding Y. Serum proteome analysis for profiling protein markers associated with lymph node metastasis in colorectal carcinoma. J Comp Pathol. 2011;144:187–94.
Ishizuka M, Kita J, Shimoda M, Kato M, Sawada T, Kubota K. Impact of grading of liver metastasis on postoperative outcome in patients with liver metastases from colorectal cancer. Hepatogastroenterology. 2012;59:54–8.
Mehlen P, Puisieux A. Metastasis: a question of life or death. Nat Rev Cancer. 2006;6:449–58.
Roessler S, Jia HL, Budhu A, Forgues M, Ye QH, Lee JS, et al. A unique metastasis gene signature enables prediction of tumor relapse in early-stage hepatocellular carcinoma patients. Cancer Res. 2010;70:10202–12.
Armaghany T, Wilson JD, Chu Q, Mills G. Genetic alterations in colorectal cancer. Gastrointest Cancer Res. 2012;5:19–27.
Benson 3rd AB, Arnoletti JP, Bekaii-Saab T, Chan E, Chen YJ, Choti MA, et al. Colon cancer. J Natl Compr Cancer Netw. 2011;9:1238–90.
Yamaguchi Y, Hotta K, Imai K, Kakushma N, Ono H. Recurrence after curative surgical resection of T1 rectal cancer: a report of two cases. Dig Endosc. 2013;25:26–30.
Siegel R, Naishadham D, Jemal A. Cancer statistics, 2012. CA Cancer J Clin. 2012;62:10–29.
Hannun YA, Obeid LM. Principles of bioactive lipid signalling: lessons from sphingolipids. Nat Rev Mol Cell Biol. 2008;9:139–50.
Shida D, Takabe K, Kapitonov D, Milstien S, Spiegel S. Targeting SphK1 as a new strategy against cancer. Curr Drug Targets. 2008;9:662–73.
Oskeritzian CA, Alvarez SE, Hait NC, Price MM, Milstien S, Spiegel S. Distinct roles of sphingosine kinases 1 and 2 in human mast-cell functions. Blood. 2008;111:4193–200.
Liu H, Chakravarty D, Maceyka M, Milstien S, Spiegel S. Sphingosine kinases: a novel family of lipid kinases. Prog Nucleic Acid Res Mol Biol. 2002;71:493–511.
Xun C, Chen MB, Qi L, Tie-Ning Z, Peng X, Ning L, et al. 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.
Miller AV, Alvarez SE, Spiegel S, Lebman DA. Sphingosine kinases and sphingosine-1-phosphate are critical for transforming growth factor beta-induced extracellular signal-regulated kinase 1 and 2 activation and promotion of migration and invasion of esophageal cancer cells. Mol Cell Biol. 2008;28:4142–51.
Lieberman DA, Rex DK, Winawer SJ, Giardiello FM, Johnson DA, Levin TR. Guidelines for colonoscopy surveillance after screening and polypectomy: a consensus update by the US Multi-Society Task Force on Colorectal Cancer. Gastroenterology. 2012;143:844–57.
Perencevich M, Stoffel EM. A multidisciplinary approach to the diagnosis and management of multiple colorectal polyps. Gastroenterol Hepatol. 2011;7:420.
Mizutani N, Omori Y, Tanaka K, Ito H, Takagi A, Kojima T, et al. Murate T increased SPHK2 transcription of human colon cancer cells in serum-depleted culture: the involvement of CREB transcription factor. J Cell Biochem. 2015;116(10):2227–38.
French KJ, Zhuang Y, Maines LW, Gao P, Wang W, Beljanski V, et al. Pharmacology and antitumor activity of ABC294640, a selective inhibitor of sphingosine kinase-2. J Pharmacol Exp Ther. 2010;333:129–39.
Fidler IJ, Hart IR. Biological diversity in metastatic neoplasms: origins and implications. Science. 1982;217:998–1003.
Liotta LA, Steeq PS, Stetler-Stevenson WG. Cancer metastasis and angiogenesis: an imbalance of positive and negative regulation. Cell. 1991;64:327–36.
Dang CV. MYC on the path to cancer. Cell 2012;149:22–35 24, Ott CJ, Kopp N, Bird L, Paranal RM, Qi J, Bowman T, et al. BET bromodomain inhibition targets both c-MYC and IL7R in high-risk acute lymphoblastic leukemia. Blood. 2012;120:2843–5.
Gaundar SS, Bradstock KF, Bendall LJ. p38MAPK inhibitors attenuate cytokine production by bone marrow stromal cells and reduce stroma-mediated proliferation of acute lymphoblastic leukemia cells. Cell Cycle. 2009;8:2975–83.
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This work is supported by science research project foundation of Liaoning province (No: L2014338)
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Zhang, L., Liu, X., Zuo, Z. et al. Sphingosine kinase 2 promotes colorectal cancer cell proliferation and invasion by enhancing MYC expression. Tumor Biol. 37, 8455–8460 (2016). https://doi.org/10.1007/s13277-015-4700-8
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DOI: https://doi.org/10.1007/s13277-015-4700-8