%0 Journal Article
%A Zou, Xiaoping
%A Nie, Shuang
%A Cao, Jing
%A Shi, Mengyue
%A Schuck, Kathleen
%A Shi, Zhao
%A Zhang, Lingling
%A Li, Hongzhen
%A Sun, Yifeng
%A Fang, Chao
%A Hu, Jingxiong
%A Niu, Yiqi
%A Yu, Yuanyuan
%A Zhang, Zhiheng
%A Li, Chao
%A Hu, Mingyue
%A Wang, Lei
%A Jiang, Kuirong
%A Lu, Zipeng
%A Akkan, Jan
%A Raulefs, Susanne
%A Kahlert, Christoph
%A Roth, Susanne
%A Herr, Ingrid
%A Wan, Yuan
%A Mihaljevic, Andre
%A Qian, Xuetian
%A Zhang, Qi
%A Wang, Maggie Haitian
%A Kleeff, Jörg
%A Friess, Helmut
%A Gu, Zuguang
%A Michalski, Christoph W
%A Shen, Shanshan
%A Kong, Bo
%T ALDH1A3 promotes aggressive basal-like pancreatic cancer through an AP-1/RUNX2 enhancer network.
%J Oncogene
%V nn
%@ 0950-9232
%C London
%I Springer Nature
%M DKFZ-2025-01662
%P nn
%D 2025
%Z epub
%X The basal-like transcriptional subtype of pancreatic ductal adenocarcinoma (PDAC) is linked to therapy resistance and poor prognosis. The cancer stem cell marker aldehyde dehydrogenase 1A3 (ALDH1A3) is a critical enzyme in acetaldehyde metabolism, but the interconnection to the basal-like subtype is poorly understood. Here, we identified ALDH1A3 as a key gene, which correlates with reduced survival and increased tumor growth. Functional studies revealed interaction of ALDH1A3 with genes like FAM3C, MCC, PMEPA1, and IRS2, forming a network driving PDAC progression. Chromatin profiling showed that ALDH1A3 affects acetylation of histone 3, mediating AP-1 activity, particularly via FOS family members, activating oncogenic pathways such as MAPK and TNF signaling. RUNX2 emerged as a therapeutic target within this network, as its knockdown disrupted MAPK signaling and reduced tumor growth. These findings emphasize the role of ALDH1A3 in linking nuclear metabolic-epigenetic programming in basal-like PDAC, highlighting it as a promising therapeutic target for novel treatment strategies.
%F PUB:(DE-HGF)16
%9 Journal Article
%$ pmid:40781158
%R 10.1038/s41388-025-03530-w
%U https://inrepo02.dkfz.de/record/303449