ABSTRACT
As an essential amino acid, tryptophan (Trp) has various physiological functions and is of great significance in the metabolic process of tumors. In the human body, tryptophan is mainly transformed through kynurenine metabolic pathway, which not only promotes the inherent malignant properties of tumor cells, but also leads to immune-suppressive tumor microenvironment. Changes in tryptophan metabolism often occur in tumors, accompanied by abnormal gene expression of tryptophan-related enzymes, among which indoleamine 2,3-bioxygenase (IDO)-related gene expression and tryptophan 2,3-dioxygenase (TDO)-related gene changes are the most significant. A large number of clinical trials on IDO inhibitors, TDO inhibitors and combination therapy have been carried out. This paper reviewed the tryptophan metabolic pathway, regulation of IDO (TDO), kynurenine (KYN) and other related genes in tumor cells, and outlined the development of therapeutic schedule targeting tryptophan-related genes. The new progress provides new ideas for the further exploration of tumor treatment options.
ABSTRACT
Tryptophan 2,3-dioxygnease 2 (TDO2) is specific for metabolizing tryptophan to kynurenine (KYN), which plays a critical role in mediating immune escape of cancer. Although accumulating evidence demonstrates that TDO2 overexpression is implicated in the development and progression of multiple cancers, its tumor-promoting role in esophageal squamous cell carcinoma (ESCC) remains unclear. Here, we observed that TDO2 was overexpressed in ESCC tissues and correlated significantly with lymph node metastasis, advanced clinical stage, and unfavorable prognosis. Functional experiments showed that TDO2 promoted tumor cell proliferation, migration, and colony formation, which could be prevented by inhibition of TDO2 and aryl hydrocarbon receptor (AHR). Further experimentation demonstrated that TDO2 could promote the tumor growth of KYSE150 tumor-bearing model, tumor burden of C57BL/6 mice with ESCC induced by 4-NQO, enhance the expression of phosphorylated AKT, with subsequent phosphorylation of GSK3
ABSTRACT
Tryptophan-kynurenine metabolic pathways are involved in a series of enzymatic reactions,generate a variety of bioactive compounds and participate in some complex pathophysiological processes.In recent years,studies have shown that kynurenine metabolic pathways may be associated with the pathogenesis of migraine and treatment.This article reviews the advances in research on the relationship between tryptophankynurenine metabolic pathways and migraines.