Transcription factor BACH1 promotes epithelial-mesenchymal transition by repressing iron metabolism-related genes.

Biochemical and biophysical research communications [Biochem Biophys Res Commun] 2025 Jun 30; Vol. 767, pp. 151898. Date of Electronic Publication: 2025 Apr 26.

Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
Pancreatic adenocarcinoma (PDAC) is one of the cancers with a very poor prognosis for its highly invasive and metastatic ability. Epithelial-mesenchymal transition (EMT) is critical for metastasis and invasion of PDAC cells, in which the expression of epithelial genes, such as E-cadherin (CDH1), decreases and that of mesenchymal genes increases. Transcription factor BTB and CNC homology 1 (BACH1) promotes EMT of PDAC cells in part by indirectly suppressing the expression of CDH1. However, the mechanism behind this is not yet clear. Considering recent reports on a link between intracellular iron and CDH1 expression in cancer cells, we examined whether BACH1 represses CDH1 expression by regulating ferritin gene. When AsPC-1 PDAC cells were treated with the iron chelator deferasirox (DFX), CDH1 expression was increased. While BACH1 knockdown resulted in increased CDH1 expression, combined knockdown of BACH1 and ferritin heavy chain gene (FTH1) reversed CDH1 expression. Tank-binding kinase 1 (TBK1), an upstream regulator of BACH1, was necessary to maintain EMT gene expression patterns in AsPC-1 cells. TBK1 was redundant with BACH1 to maintain VIM expression in SW1990 PDAC cells, suggesting its BACH1-independent role in EMT. Therefore, the regulation of CDH1 and EMT by BACH1 involves FTH1 and intracellular iron as mediators and TBK1 as an upstream and parallel regulator.
(Copyright © 2025 The Authors. Published by Elsevier Inc. All rights reserved.)

English

Publisher: Elsevier Country of Publication: United States NLM ID: 0372516 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1090-2104 (Electronic) Linking ISSN: 0006291X NLM ISO Abbreviation: Biochem Biophys Res Commun Subsets: MEDLINE

Epithelial-Mesenchymal Transition*/genetics , Basic-Leucine Zipper Transcription Factors*/metabolism , Basic-Leucine Zipper Transcription Factors*/genetics , Iron*/metabolism , Pancreatic Neoplasms*/metabolism , Pancreatic Neoplasms*/pathology , Pancreatic Neoplasms*/genetics , Fanconi Anemia Complementation Group Proteins*/metabolism , Fanconi Anemia Complementation Group Proteins*/genetics, Humans ; Cell Line, Tumor ; Cadherins/genetics ; Cadherins/metabolism ; Antigens, CD/genetics ; Antigens, CD/metabolism ; Gene Expression Regulation, Neoplastic ; Ferritins/genetics ; Ferritins/metabolism ; Deferasirox/pharmacology ; Protein Serine-Threonine Kinases/metabolism ; Protein Serine-Threonine Kinases/genetics ; Oxidoreductases

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