β-catenin-IRP2-primed iron availability to mitochondrial metabolism is druggable for active β-catenin-mediated cancer.

ABSTRACT:

Background

Although β-catenin signaling cascade is frequently altered in human cancers, targeting this pathway has not been approved for cancer treatment.

Methods

High-throughput screening of an FDA-approved drug library was conducted to identify therapeutics that selectively inhibited the cells with activated β-catenin. Efficacy of iron chelator and mitochondrial inhibitor was evaluated for suppression of cell proliferation and tumorigenesis. Cellular chelatable iron levels were measured to gain insight into the potential vulnerability of β-catenin-activated cells to iron deprivation. Extracellular flux analysis of mitochondrial function was conducted to evaluate the downstream events of iron deprivation. Chromatin immunoprecipitation, real-time quantitative PCR and immunob

SUBMITTER: Wu Y 

PROVIDER: S-EPMC9879242 | biostudies-literature | 2023 Jan

REPOSITORIES: biostudies-literature