| First Author | Liang J | Year | 2013 |
| Journal | Cancer Cell | Volume | 23 |
| Issue | 1 | Pages | 107-20 |
| PubMed ID | 23273921 | Mgi Jnum | J:194356 |
| Mgi Id | MGI:5473472 | Doi | 10.1016/j.ccr.2012.11.013 |
| Citation | Liang J, et al. (2013) Sphingosine-1-phosphate links persistent STAT3 activation, chronic intestinal inflammation, and development of colitis-associated cancer. Cancer Cell 23(1):107-20 |
| abstractText | 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-kappaB-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-kappaB/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-kappaB and STAT3 and connects chronic inflammation and CAC. |
