@Article{biocell.2026.075492,
AUTHOR = {Xing-Guo Li, Lu-Kai Wang, Fu-Ming Tsai, Hsueh-Chun Wang},
TITLE = {Emerging Role of ACOD1/Itaconate in Cancer: Bridging Metabolic Reprogramming and Signaling in the Tumor Microenvironment},
JOURNAL = {BIOCELL},
VOLUME = {},
YEAR = {},
NUMBER = {},
PAGES = {{pages}},
URL = {http://www.techscience.com/biocell/online/detail/25869},
ISSN = {1667-5746},
ABSTRACT = {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.},
DOI = {10.32604/biocell.2026.075492}
}