Unknown

Dataset Information

0

Sphingosine-1-phosphate links persistent STAT3 activation, chronic intestinal inflammation, and development of colitis-associated cancer.


ABSTRACT: 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-?B-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-?B/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-?B and STAT3 and connects chronic inflammation and CAC.

SUBMITTER: Liang J 

PROVIDER: S-EPMC3578577 | BioStudies | 2013-01-01

REPOSITORIES: biostudies

Similar Datasets

2017-01-01 | S-EPMC5650392 | BioStudies
1000-01-01 | S-EPMC2860904 | BioStudies
2019-01-01 | S-EPMC6560353 | BioStudies
2018-01-01 | S-EPMC6321283 | BioStudies
2015-01-01 | S-EPMC4463432 | BioStudies
2011-01-01 | S-EPMC3212543 | BioStudies
2016-01-01 | S-EPMC5773104 | BioStudies
2020-01-01 | S-EPMC7217063 | BioStudies
2015-01-01 | S-EPMC4580500 | BioStudies
2014-01-01 | S-EPMC4347220 | BioStudies