Hepcidin sequesters iron to sustain nucleotide metabolism and mitochondrial function in colorectal cancer epithelial cells.

ABSTRACT: Colorectal cancer (CRC) requires massive iron stores, but the complete mechanisms by which CRC modulates local iron handling are poorly understood. Here, we demonstrate that hepcidin is activated ectopically in CRC. Mice deficient in hepcidin specifically in the colon tumour epithelium, compared with wild-type littermates, exhibit significantly diminished tumour number, burden and size in a sporadic model of CRC, whereas accumulation of intracellular iron by deletion of the iron exporter ferroportin exacerbates these tumour parameters. Metabolomic analysis of three-dimensional patient-derived CRC tumour enteroids indicates a prioritization of iron in CRC for the production of nucleotides, which is recapitulated in our hepcidin/ferroportin mouse CRC models. Mechanistically, our data suggest

SUBMITTER: Schwartz AJ 

PROVIDER: S-EPMC8316354 | biostudies-literature | 2021 Jul

REPOSITORIES: biostudies-literature