Transferrin Receptor-Mediated Iron Uptake Promotes Colon Tumorigenesis.

ABSTRACT: Transferrin receptor (TFRC) is the major mediator for iron entry into a cell. Under excessive iron conditions, TFRC is expected to be reduced to lower iron uptake and toxicity. However, the mechanism whereby TFRC expression is maintained at high levels in iron-enriched cancer cells and the contribution of TFRC to cancer development are enigmatic. Here the work shows TFRC is induced by adenomatous polyposis coli (APC) gene loss-driven β-catenin activation in colorectal cancer, whereas TFRC-mediated intratumoral iron accumulation potentiates β-catenin signaling by directly enhancing the activity of tankyrase. Disruption of TFRC leads to a reduction of colonic iron levels and iron-dependent tankyrase activity, which caused stabilization of axis inhibition protein 2 (AXIN2) and subsequent repr

SUBMITTER: Kim H 

PROVIDER: S-EPMC10074045 | biostudies-literature | 2023 Apr

REPOSITORIES: biostudies-literature