M⁶A demethylase FTO drives pancreatic ductal adenocarcinoma tumorigenesis and metastasis through remodeling PFKM mediated glycolysis.

ABSTRACT: N6-methyladenosine (m⁶A) modification has emerged as a common chemical modification in epigenetic regulation. However, whether this m⁶A modification is involved in glycolysis metabolism in pancreatic ductal adenocarcinoma (PDAC) remains elusive. Multiomics integration strategies, including metabolomics, m⁶A-seq and transcriptome sequencing, were utilized to evaluate the associations between m⁶A modifications and key processes of glucose metabolism in PDAC. Spontaneous PDAC mice (LSLKras^G12D/+, LSL-Trp53^R172H/+, Pdx1-Cre; KPC) with FTO-conditional knockout and organoids were used to evaluate the effects of FTO stimulation on PDAC cell glycolysis and tumorigenesis. Series of in vivo and vitro functional analysis revealed that

SUBMITTER: Tan Z 

PROVIDER: S-EPMC12583531 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature