Role of tryptophan metabolism and the AHR on breast cancer
DOI:
https://doi.org/10.32776/revbiomed.v37.i2.1369Keywords:
Aryl Hydrocarbon Receptor, kynurenin, breast cancerAbstract
Breast cancer (BC) is one of the most common malignancies among women worldwide. In BC, cells increase their metabolism by regulating multiple metabolic pathways. In this descriptive review, recent literature indexed in PubMed was reviewed, and the current state of knowledge on tryptophan (Trp) metabolism, the kynurenine (Kyn) pathway and its derived metabolites, their relationship with aryl hydrocarbon receptor (AHR)-mediated signaling in BC, and their potential as a therapeutic target was discussed. Three Trp catabolism enzymes are overexpressed in breast cancer: indolamine-2,3-dioxygenase 1 and 2 (IDO1/2) and tryptophan-2,3-dioxygenase 2 (TDO2). They catalyze the degradation step from Trp to Kyn an AHR ligand. The AHR is a transcription factor characterized by its role in mediating toxicity and adaptive responses to polycyclic aromatic hydrocarbons and has been detected overexpressed in breast tumors. Kyn and other metabolites derived from Trp activate signaling pathways through the AHR, which stimulates IDO1 expression, increasing Kyn levels and promoting an immunosuppressive circuit. Furthermore, substantial evidence has shown that this mechanism drives the progression of BC. The idea of inhibiting these molecules has aroused great expectations to find new drugs for BC therapy.
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