TY  - EJOU
AU  - Li, Xing-Guo 
AU  - Wang, Lu-Kai 
AU  - Tsai, Fu-Ming 
AU  - Wang, Hsueh-Chun 

TI  - Emerging Role of ACOD1/Itaconate in Cancer: Bridging Metabolic Reprogramming and Signaling in the Tumor Microenvironment
T2  - BIOCELL

PY  - 
VL  - 
IS  - 
SN  - 1667-5746

AB  - Itaconate, produced by aconitate decarboxylase 1 (ACOD1, also known as IRG1), acts as a key immunometabolite that inhibits succinate dehydrogenase (SDH) and can engage reduction-oxidation (redox)-sensitive signaling programs. This review summarizes the emerging, context-dependent roles of the ACOD1-itaconate axis in cancer, while critically distinguishing between the effects of endogenous itaconate and its cell-permeable derivatives. In tumor cells, endogenous <i>ACOD1</i> expression or uptake via solute carrier family 13 member 3 (SLC13A3) alters oxidative phosphorylation and glycolysis. In the tumor microenvironment, myeloid-derived itaconate contributes to immune tolerance by reducing dendritic-cell cross-priming and limiting CD8<sup>+</sup> T-cell metabolic activity. Moreover, interactions between ACOD1-derived endogenous itaconate and stress-responsive signaling pathways, including Extracellular Signal-Regulated Kinase (ERK)1/2 and AMP-activated Protein Kinase (AMPK), couple mitochondrial metabolic perturbation to adaptive cellular responses, whereas electrophilic itaconate derivatives can additionally engage ERK- and Nuclear Factor Erythroid 2-related factor 2 (NRF2)-linked cytoprotective programs. Collectively, these findings highlight the ACOD1/itaconate axis as a context-dependent node of metabolic control, offering new perspectives for a stratified therapeutic approach based on tumor lineage and transporter expression.
KW  - Aconitate decarboxylase 1; AMP-activated protein kinase; itaconate; cancer; extracellular signal-regulated kinase; mitochondrial metabolism; nuclear factor erythroid 2-related factor 2; reduction-oxidation signaling

DO  - 10.32604/biocell.2026.075492