Sphingosine kinase and sphingosine-1-phosphate receptor signaling pathway in inflammatory gastrointestinal disease and cancers: A novel therapeutic target

Publication date: Available online 18 December 2019Source: Pharmacology & TherapeuticsAuthor(s): Olga A. Sukocheva, Hideki Furuya, Mei Li Ng, Markus Friedemann, Mario Menschikowski, Vadim V. Tarasov, Vladimir N. Chubarev, Sergey G. Klochkov, Margarita E. Neganova, Arduino A. Mangoni, Gjumrakch Aliev, Anupam BishayeeAbstractInflammatory gastrointestinal (GI) diseases and malignancies are associated with growing morbidity and cancer-related mortality worldwide. GI tumor and inflammatory cells contain activated sphingolipid-metabolizing enzymes, including sphingosine kinase 1 (SphK1) and SphK2, that generate sphingosine-1-phosphate (S1P), a highly bioactive compound. Many inflammatory responses, including lymphocyte trafficking, are directed by circulatory S1P, present in high concentrations in both the plasma and the lymph of cancer patients. High fat and sugar diet, disbalanced intestinal flora, and obesity have recently been linked to activation of inflammation and SphK/S1P/S1P receptor (S1PR) signaling in various GI pathologies, including cancer. SphK1 overexpression and activation facilitate and enhance the development and progression of esophageal, gastric, and colon cancers. SphK/S1P axis, a mediator of inflammation in the tumor microenvironment, has recently been defined as a target for the treatment of GI disease states, including inflammatory bowel disease and colitis. Several SphK1 inhibitors and S1PR antagonists have been developed as novel anti-inflammatory and anti...
Source: Pharmacology and Therapeutics - Category: Drugs & Pharmacology Source Type: research