Intestinal Epithelial Deletion of Sphk1 Prevents Colitis-Associated Cancer Development by Inhibition of Epithelial STAT3 Activation
| Autor: | Seung Bin Park, Yoon Seok Noh, Yoon A. Jeong, Hyo Jung Kim, Byung Il Choi, Jong Jae Park, Moon Kyung Joo, Hyunjoo Lee, Beom Jae Lee, Nam Joo Kim, Jae Seon Kim |
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| Rok vydání: | 2019 |
| Předmět: |
STAT3 Transcription Factor
Physiology Carcinogenesis Inflammatory bowel disease 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine medicine Animals Humans Colitis STAT3 Mice Knockout Oncogene Sphingosine biology Carcinoma Dextran Sulfate Gastroenterology Cancer Interleukin Epithelial Cells medicine.disease HCT116 Cells Phosphotransferases (Alcohol Group Acceptor) chemistry 030220 oncology & carcinogenesis Colonic Neoplasms Cancer research biology.protein 030211 gastroenterology & hepatology Signal transduction |
| Zdroj: | Digestive diseases and sciences. 65(8) |
| ISSN: | 1573-2568 |
| Popis: | Colitis-associated cancer (CAC) is one of the most serious complications in patients with inflammatory bowel disease. Sphingosine kinase 1 (Sphk1) is a key enzyme in the sphingolipid pathway and has oncogene potential for inducing both initiation and progression of tumors. The aim of this work is to characterize the role of epithelial Sphk1 in mouse colitis and CAC models. We investigated the roles of Sphk1 in CAC by conditional deletion of Sphk1 in intestinal epithelial cells (IECs). CAC was induced in both Sphk1ΔIEC/ApcMin/+ and Sphk1IEC/ApcMin/+ mice by administration of 2% dextran sodium sulfate (DSS) for 7 days. Genetic deletion of Sphk1 significantly reduced the number and size of tumors in ApcMin/+ mice. Histologic grade was more severe in Sphk1ΔIEC/ApcMin/+ mice compared with Sphk1IEC/ApcMin/+ mice (invasive carcinoma, 71% versus 13%, p |
| Databáze: | OpenAIRE |
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