The DOI matches its Crossref record; 61 of the 62 references it cites were found in a registry or an index.
Sphingosine-1-Phosphate Links Persistent STAT3 Activation, Chronic Intestinal Inflammation, and Development of Colitis-Associated Cancer
Open accessAbstract
Inflammatory bowel disease is an important risk factor for colorectal cancer. We show that sphingosine-1-phosphate (S1P) produced by upregulation of sphingosine kinase 1 (SphK1) links chronic intestinal inflammation to colitis-associated cancer (CAC) and both are exacerbated by deletion of Sphk2. S1P is essential for production of the multifunctional NF-κB-regulated cytokine IL-6, persistent activation of the transcription factor STAT3, and consequent upregulation of the S1P receptor, S1PR1. The prodrug FTY720 decreased SphK1 and S1PR1 expression and eliminated the NF-κB/IL-6/STAT3 amplification cascade and development of CAC, even in Sphk2(-/-) mice, and may be useful in treating colon cancer in individuals with ulcerative colitis. Thus, the SphK1/S1P/S1PR1 axis is at the nexus between NF-κB and STAT3 and connects chronic inflammation and CAC.
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“STAT3 is also involved in inflammation-associated carcinogenesis, suppression of the antitumor immune response, and maintenance of cancer stem cells.”
From Critical analysis of the potential for targeting STAT3 in human malignancy (2013) · cites this paper as [95]
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“This process is critically involved in colitis-associated cancer (310).”
From IL-6 in inflammation, autoimmunity and cancer (2021) · cites this paper as [310]
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1 retracted
Histone Deacetylase Inhibitors Suppress the Induction of c-Jun and Its Target Genes Including COX-2
Yamaguchi, K., Lantowski, A., Dannenberg, A. J., & Subbaramaiah, K. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m503201200 · Cited by 80
RetractedImmunity, Inflammation, and Cancer
Grivennikov, S. I., Greten, F. R., & Karin, M. (2010) · Cell · doi:10.1016/j.cell.2010.01.025 · Cited by 10,755
STATs in cancer inflammation and immunity: a leading role for STAT3
Yu, H., Pardoll, D., & Jove, R. (2009) · Nature reviews. Cancer · doi:10.1038/nrc2734 · Cited by 4,383
IKKβ Links Inflammation and Tumorigenesis in a Mouse Model of Colitis-Associated Cancer
Greten, F. R., Eckmann, L., Greten, T. F., Park, J. M., Li, Z.-W., Egan, L. J., Kagnoff, M. F., & Karin, M. (2004) · Cell · doi:10.1016/j.cell.2004.07.013 · Cited by 2,433
Oshima, M., Dinchuk, J. E., Kargman, S., Oshima, H., Hancock, B. C., Kwong, E. C., Trzăskos, J. M., Evans, J. F., & Taketo, M. M. (1996) · Cell · doi:10.1016/s0092-8674(00)81988-1 · Cited by 2,363
Grivennikov, S., Karin, E., Terzic, J., Mucida, D., Yu, G.-Y., Vallabhapurapu, S., Scheller, J., Rose-John, S., Cheroutre, H., Eckmann, L., et al. (2009) · Cancer Cell · doi:10.1016/j.ccr.2009.01.001 · Cited by 2,155
Wu, S., Rhee, K.-J., Albesiano, E., Rabizadeh, S., Wu, X., Yen, H.-R., Huso, D. L., Brancati, F. L., Wick, E., McAllister, F., et al. (2009) · Nature Medicine · doi:10.1038/nm.2015 · Cited by 1,812
Inflammation meets cancer, with NF-κB as the matchmaker
Ben‐Neriah, Y., & Karin, M. (2011) · Nature Immunology · doi:10.1038/ni.2060 · Cited by 1,412
Fingolimod (FTY720): discovery and development of an oral drug to treat multiple sclerosis
Brinkmann, V., Billich, A., Baumruker, T., Heining, P., Schmouder, R., Francis, G., Aradhye, S., & Burtin, P. (2010) · Nature Reviews Drug Discovery · doi:10.1038/nrd3248 · Cited by 1,273
Takeda, K., Clausen, B. E., Kaisho, T., Tsujimura, T., Terada, N., Förster, I., & Akira, S. (1999) · Immunity · doi:10.1016/s1074-7613(00)80005-9 · Cited by 1,220
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(2016) · Wiley eBooks · doi:10.1002/9783527685059.ch2 · Cited by 2
Huang, H., Duan, B., Huang, Z., Wang, S., Wen, Y., Jiang, Q., Chen, P.-Y., Huang, P., Liu, J., Zheng, S., et al. (2024) · Rapid Communications in Mass Spectrometry · doi:10.1002/rcm.9939 · Cited by 1
Kaur, P., Karuppuchamy, T., Chilukuri, A., Kim, M., Urrete, J., Shen, Z., Saxon, L., Lundborg, L. R., Mikulski, Z., Jedlicka, P., et al. (2025) · Inflammatory Bowel Diseases · doi:10.1093/ibd/izaf030 · Cited by 1
The Role of Diet in Crohn’s Disease: From Etiology to Evidence-Based Management
Jamal, F., Alatout, M. H., Khan, M. A., Pasha, S. B., & Malik, T. A. (2025) · Cureus · doi:10.7759/cureus.86891 · Cited by 1
Navarrete, P. I. R., Collotta, D., Bello, F. D., Cento, A. S., Aragno, M., Collino, M., & Mastrocola, R. (2025) · The Journal of Nutritional Biochemistry · doi:10.1016/j.jnutbio.2025.110068 · Cited by 1
Targeting Interleukin‐6 as a Novel Strategy to Overcome Eribulin Resistance in Breast Cancer
Hattori, A., Nagahashi, M., Komatsu, M., Urano, S., Kuroiwa, M., Matsushita, Y., Katagiri, T., Shimoda, M., & Miyoshi, Y. (2025) · Cancer Medicine · doi:10.1002/cam4.71273 · Cited by 2
Self-citationJeon, J., Kang, J., Park, J., Lee, J.-H., Kim, D. E., Park, W., & Kim, S. (2026) · PLoS ONE · doi:10.1371/journal.pone.0340437 · Cited by 1
Colon Cancer: The Role of Sphingolipid Metabolic Enzymes
Furuya, H., Choi, S., Obeid, L. M., Kawamori, T., & Snider, A. J. (2015) · Springer eBooks · doi:10.1007/978-3-319-20750-6_7 · Cited by 1
Sphingosine-1-phosphate, its receptors, and their role in multiple sclerosis
COHAN, S. L., & Chen, C. (2023) · Elsevier eBooks · doi:10.1016/b978-0-443-18578-6.00009-x · Cited by 1
Zakaria, Z., Othman, Z. A., Kamaruzaman, K. A., & Mohamed, M. (2024) · Advances in biochemistry in health and disease · doi:10.1007/978-3-031-55474-2_5 · Cited by 1
Waltl, L., Holubek, D., Speck, K., Wildermuth, R., Haut, F., Permann, S., Plangger, I., Steinborn, C., Rao, Z., D’Avino, D., et al. (2026) · Advanced Science · doi:10.1002/advs.76861 · Cited by 1
Dhanabalan, A. K., Velmurugan, D., Haribabu, J., & Gunasekaran, K. (2024) · Molecular Diversity · doi:10.1007/s11030-024-10997-4 · Cited by 1
Aspirin: a modern view of a well-known medicine (review)
Palibroda, N. M., Butnaru, M. Y., & Lavrova, O. I. (2018) · Bukovinian Medical Herald · doi:10.24061/2413-0737.xxii.2.86.2018.48 · Cited by 1
STAT3 polymorphisms in North Africa and its implication in breast cancer
Ziadi, W., Boussetta, S., Elkamel, S., PAKSTIS, A. J., Kídd, K. K., Medimegh, I., Elgaaïed, A. B. A., & Cherni, L. (2021) · Molecular Genetics & Genomic Medicine · doi:10.1002/mgg3.1744 · Cited by 1
Physiological and Pharmacological Regulation of the STAT3 Pathway in Cancer
Xiang, M. H. (2013) · Digital Access to Scholarship at Harvard (DASH) (Harvard University) · Cited by 1
Haddadi, N. (2019) · OPUS - Open Publications of UTS Scholars (University of Technology Sydney) · Cited by 1
Yamada, A., Spiegel, S., & Takabe, K. (2015) · Encyclopedia of Inflammatory Diseases · doi:10.1007/978-3-0348-0620-6_197-2 · Cited by 1
Self-citationTaylor, O., DeGroff, N., El‐Hodiri, H. M., Gao, C., & Fischer, A. J. (2024) · eLife · doi:10.7554/elife.102151.1 · Cited by 1
Taylor, O., Kelly, L. E., El‐Hodiri, H. M., & Fischer, A. J. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2025.02.03.636254 · Cited by 1
Taylor, O., DeGroff, N., El‐Hodiri, H. M., Gao, C., & Fischer, A. J. (2025) · eLife · doi:10.7554/elife.102151.3 · Cited by 1
Hot on the TRAIL: Targeting SPHK1 in Colorectal Cancer: Therapeutic Potential of PF-543
Chen, Z., & Sun, X. (2025) · Digestive Diseases and Sciences · doi:10.1007/s10620-025-09384-2 · Cited by 1
Nguyen, A. V., Wu, Y., & Lin, E. Y. (2015) · AIMS molecular science · doi:10.3934/molsci.2015.1.34
Acetylsalicylsäure und Prävention kolorektaler Karzinome
Schrör, K., & Rauch, B. H. (2014) · coloproctology · doi:10.1007/s00053-013-0417-6
Stem Cell Transplantation for Crohn’s Disease
Liang, J., & Wu, K. (2015) · Translational medicine research · doi:10.1007/978-94-017-7273-0_18
Self-citationSpiegel, S. (2015)
Self-citationTranscription Factors and Colorectal Cancer: An Overview
Allam, U. S., Kamatham, S., Adarsha, M., Jasmine, S. M., & Prasad, P. V. G. (2017) · Springer eBooks · doi:10.1007/978-981-10-6728-0_15
Regulation of lysophosphatidate-induced mechanisms of chemo-resistance
Venkatraman, G. (2015) · ERA: Education and Research Archive (University of Alberta) · doi:10.7939/r3bn9x79k
KANSER GELİŞİMİNDE İNFLAMASYONUN ROLÜ
Yıldırım, I. (2019) · ANADOLU UNIVERSITY JOURNAL OF SCIENCE AND TECHNOLOGY –C Life Sciences and Biotechnology · doi:10.18036/aubtdc.412520
WITHDRAWN: Ceramide and Sphingosine 1-Phosphate in adipose dysfunction
Fang, Z., Pyne, S., & Pyne, N. J. (2019) · Progress in Lipid Research · doi:10.1016/j.plipres.2019.100991
Clinical Applications of Aspirin
Schrör, K. (2016) · Wiley eBooks · doi:10.1002/9783527685059.ch4
Faculty Opinions recommendation of Sphingolipid metabolism in cancer signalling and therapy.
Loughran, T. P., & Tan, S. (2018) · Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature · doi:10.3410/f.732125735.793546487
Torres, L. A. T. (2022) · Digital Library of Theses and Dissertations (Universidade de São Paulo) · doi:10.11606/d.60.2022.tde-21032022-112723
Schrör, K. (2022) · De Gruyter eBooks · doi:10.1515/9783110746419-002
Taylor, O., DeGroff, N., El‐Hodiri, H. M., Gao, C., & Fischer, A. J. (2025) · eLife · doi:10.7554/elife.102151.2
Role of erythrocyte Gq protein in tumor metastasis
Vučetić, A. (2025) · doi:10.21248/gups.91215
Xue, Y., Jiang, W., Ma, Q., Wang, X., Jia, P., Li, Q., Chen, S., Song, B., Wang, Y., Zhang, J., et al. (2020) · Figshare · doi:10.6084/m9.figshare.12432311
Chang, Y.-C., Liu, H.-P., Chuang, H.-L., Liao, J.-W., Kao, P.-L., Chan, H.-L., Chen, T.-H., & Wang, Y.-C. (2023) · Figshare · doi:10.6084/m9.figshare.24531975
Takanashi, Y., Kahyo, T., Sekihara, K., Kawase, A., Setou, M., & Funai, K. (2024) · Figshare · doi:10.6084/m9.figshare.25903898
Jeong, D.-W., Lee, S., & Chun, Y.-S. (2021) · Figshare · doi:10.6084/m9.figshare.17010237
Loss of Acid Ceramidase in Myeloid Cells Protects from Chronic Colitis in IL10-Deficent MicePreprint
Espinoza, K. S., Dahl, B. K., Wysong, J. N., Ryan, E. M., Gordon, M. R., Doll, C. L., Marron, M. T., Beard, C. A., Dey, P. D., Simpson, R. J., et al. (2026) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2026.01.05.697503
shaoping, W., Gao, D., Xiaoyi, Z., Qinzhong, L., Dong, D., Pang, Y., Zhongwei, L., & Ganghua, L. (2026) · Research Square · doi:10.21203/rs.3.rs-8730826/v1
Bao, W.-Q., Xu, T.-T., Huang, B.-Q., Li, S.-Q., Jiang, M., Ma, G.-Y., Zhang, C., Chen, L., Li, D., Zhou, N., et al. (2026) · Engineering · doi:10.1016/j.eng.2026.02.033
Yoshida, M., Sato, K., Nakahata, N., Sato, H., Ohagi, R., Kanno, E., Tanno, H., イシイ, ケ., Aoyagi, T., Kikuchi, A., et al. (2026) · Infection and Immunity · doi:10.1128/iai.00612-25
Decreased PP2A expression and activity represent a therapeutic target for plexiform neurofibroma
Yue, M., Wang, Y., Gu, J., Zhang, C., Chen, Y., Gao, A., Choi, K., Wu, Z., Wang, Z., Pundavela, J., et al. (2026) · Acta Neuropathologica Communications · doi:10.1186/s40478-026-02315-w · Cited by 1
Khan, R., Allende, M. L., Khalid, E., Lee, J. Y., Stone, E. W., Rodnick-Smith, M., Izuhara, A. K., Buncha, V., Gyarmati, G., Peti‐Peterdi, J., et al. (2026) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2026.05.11.724358
Meng, S., Zhang, D., Baokan, J., Xu, C., Tan, J., Lai, Y., Fan, M., Tao, L., Li, L., Shen, W., et al. (2026) · Journal of Ethnopharmacology · doi:10.1016/j.jep.2026.121987
Han, Q., 张潇潇, & Li, S. (2026) · Inflammation Research · doi:10.1007/s00011-026-02390-8
Silencing without clearing: pharmacological modulation of the SASP in aging and disease
Fresser, L., Chrienová, Ž., Gebrt, J., Olekšák, P., Kuča, K., & Nepovimová, E. (2026) · Frontiers in Pharmacology · doi:10.3389/fphar.2026.1911529
Loss of Acid Ceramidase in Myeloid Cells Protects From Chronic Colitis in IL10 ‐Deficient Mice
Espinoza, K. S., Dahl, B. K., Ryan, E. M., Gordon, M. R., Doll, C. L., Marron, M. T., Beard, C. A., Dey, P. D., Besselsen, D. G., Simpson, R. J., et al. (2026) · The FASEB Journal · doi:10.1096/fj.202602342rrr
Chen, Q., Wu, C., Huang, C., & Zhou, H. (2026) · MedComm · doi:10.1002/mco2.71038
Liu, S., Zhang, D., Zong, Z., Hu, Y., Bai, J., Li, J., 孙文斌, Yang, X., Chen, Y., Yang, B., et al. (2026) · Journal of Ethnopharmacology · doi:10.1016/j.jep.2026.122569
BindingDB Entry 50045019: Crystal Structure of Sphingosine Kinase 1 with PF-543.
BindingDB (2016) · UC San Diego · doi:10.7270/q22b90nm
Chokshi, N., Hok, K. D., Gunamalai, L., Chen, N. K., Shadid, A., Rich, H. E., Doursout, M., Banda, N. K., & Shivshankar, P. (2026) · Immune Network · doi:10.4110/in.2026.26.e38
PTPRT/D MUTATION OR PROMOTER METHYLATION: IMPLICATIONS FOR STAT3 INHIBITION
Peyser, N. D. (2015) · D-Scholarship@Pitt (University of Pittsburgh)
Metadata
- Authors
- Liang, J., Nagahashi, M., Kim, E. Y., Harikumar, K. B., Yamada, A., Huang, W.-C., Hait, N. C., Allegood, J. C., Price, M. M., Avni, D., Takabe, K., Kordula, T., Milstien, S., & Spiegel, S.
- Affiliations
- Virginia Commonwealth University (US)
- Corresponding author
- Spiegel, Sarah
- ORCID
- Venue
- Cancer Cell
- Publisher
- Elsevier BV
- Published
- 2013-01
- Volume
- 23
- Issue
- 1
- Pages
- 107-120
- ISSN
- 1535-6108 (ISSN-L)
- PMC
- PMC3578577
- OpenAlex
- W2145876349
- Cited by
- 563
- References
- 62
- Citations by year
- 2026: 21 · 2025: 29 · 2024: 35 · 2023: 20 · 2022: 37 · 2021: 45 · 2020: 51 · 2019: 42 · 2018: 44 · 2017: 57 · 2016: 59 · 2015: 48 · 2014: 48 · 2013: 25
- FWCI
- 15.70
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cancer Cell (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Susan G. Komen
- National Institutes of Health (5k12hd055881-05)
- Japan Society for the Promotion of Science
- National Heart, Lung, and Blood Institute (T32HL094290)
- National Cancer Institute (P30CA16059, R01CA160688, R01CA-61774, R01CA061774, P30CA016059)
- National Institute of General Medical Sciences (R37GM043880)
- National Institute of Allergy and Infectious Diseases (U19AI077435)
- National Institute of Neurological Disorders and Stroke (P30NS047463)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (K12-HD055881)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Sphingolipid Metabolism and Signaling
- Life Sciences › Immunology and Microbiology › Immunology › Cytokine Signaling Pathways and Interactions
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Lipids, and Metabolism
- Keywords
- sphingosine-1-phosphate, sphingosine kinase 1, sphingosine kinase 2, S1PR1, STAT3 activation, NF-κB, interleukin-6, colitis-associated colorectal cancer, inflammatory bowel disease, ulcerative colitis, fingolimod, chronic intestinal inflammation, colorectal cancer
- MeSH terms
- Fingolimod Hydrochloride, Sphingosine Kinase, Animals, Cell Transformation, Neoplastic, Colitis, Colon, Lysophospholipids, Propylene Glycols, Sphingosine, Interleukin-6, Gene Expression Regulation, Neoplastic, NF-kappa B, Gene Deletion, Phosphotransferases (Alcohol Group Acceptor), STAT3 Transcription Factor, Mice, Tumor Microenvironment
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