Mitochondrial Aconitase ACO2 Links Iron Homeostasis with Tumorigenicity in Non-Small Cell Lung Cancer.

ABSTRACT: The ability of a patient tumor to engraft an immunodeficient mouse is the strongest known independent indicator of poor prognosis in early-stage non-small cell lung cancer (NSCLC). Analysis of primary NSCLC proteomes revealed low-level expression of mitochondrial aconitase (ACO2) in the more aggressive, engrafting tumors. Knockdown of ACO2 protein expression transformed immortalized lung epithelial cells, whereas upregulation of ACO2 in transformed NSCLC cells inhibited cell proliferation in vitro and tumor growth in vivo. High level ACO2 increased iron response element binding protein 1 (IRP1) and the intracellular labile iron pool. Impaired cellular proliferation associated with high level ACO2 was reversed by treatment of cells with an iron chelator, whereas increased cell proliferation

SUBMITTER: Mirhadi S 

PROVIDER: S-EPMC9808373 | biostudies-literature | 2023 Jan

REPOSITORIES: biostudies-literature