Journal Article

DKFZ-2025-00462

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png The m6A demethylase FTO promotes C/EBPβ-LIP translation to perform oncogenic functions in breast cancer cells.

Zuidhof, H. R. ; Müller, C. ; Kortman, G. ; Wardenaar, R. ; Stepanova, E.DKFZ* ; Loayza-Puch, F.DKFZ* ; Calkhoven, C. F.

2025
Wiley-Blackwell Oxford [u.a.]

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Please use a persistent id in citations: doi:10.1111/febs.70033

Abstract: N6-methyladenosine (m6A) is a prevalent posttranscriptional mRNA modification involved in the regulation of transcript turnover, translation, and other aspects of RNA fate. The modification is mediated by multicomponent methyltransferase complexes (so-called writers) and is reversed through the action of the m6A-demethylases fat mass and obesity-associated (FTO) and alkB homolog 5 (ALKBH5) (so-called erasers). FTO promotes cell proliferation, colony formation and metastasis in models of triple-negative breast cancer (TNBC). However, little is known about genome-wide or specific downstream regulation by FTO. Here, we examined changes in the genome-wide transcriptome and translatome following FTO knockdown in TNBC cells. Unexpectedly, FTO knockdown had a limited effect on the translatome, while transcriptome analysis revealed that genes related to extracellular matrix (ECM) and epithelial-mesenchymal transition (EMT) are regulated through yet unidentified mechanisms. Differential translation of CEBPB mRNA into the C/EBPβ transcription factor isoform C/EBPβ-LIP is known to act in a pro-oncogenic manner in TNBC cells through regulation of EMT genes. Here we show that FTO is required for efficient C/EBPβ-LIP expression, suggesting that FTO has oncogenic functions through regulation of C/EBPβ-LIP.

Keyword(s): C/EBPβ ; FTO ; breast cancer ; mRNA translation

Note: 2025 May;292(10):2688-2709

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Contributing Institute(s):

1. B250 NWG Translationskontrolle und Stoffwechsel (B250)

Research Program(s):

1. 312 - Funktionelle und strukturelle Genomforschung (POF4-312) (POF4-312)

Appears in the scientific report 2025

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Database coverage:
; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Life Sciences ; DEAL Wiley ; Ebsco Academic Search ; Essential Science Indicators ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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