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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Cites
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
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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
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Flagged first, then by citations
1 of the 62 references couldn’t be matched to a known paper.
Cited by
Sorted by citations
Sphingolipids and their metabolism in physiology and disease
Hannun, Y. A., & Obeid, L. M. (2017) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm.2017.107 · Cited by 2,117
Inflammation-induced cancer: Crosstalk between tumours, immune cells and microorganisms
Elinav, E., Nowarski, R., Thaiss, C. A., Hu, B., Jin, C., & Flavell, R. A. (2013) · Nature reviews. Cancer · doi:10.1038/nrc3611 · Cited by 2,000
Revisiting STAT3 signalling in cancer: new and unexpected biological functions
Yu, H., Lee, H., Herrmann, A., Buettner, R., & Jove, R. (2014) · Nature Reviews Cancer · doi:10.1038/nrc3818 · Cited by 2,137
IL-6 in inflammation, autoimmunity and cancer
Hirano, T. (2021) · International Immunology · doi:10.1093/intimm/dxaa078 · Cited by 1,453
“This process is critically involved in colitis-associated cancer (310).”
BackgroundLipid metabolic reprogramming in cancer cells
Beloribi‐Djefaflia, S., Vasseur, S., & Guillaumond, F. (2016) · Oncogenesis · doi:10.1038/oncsis.2015.49 · Cited by 1,418
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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