TY  - JOUR
AU  - Zou, Xiaoping
AU  - Nie, Shuang
AU  - Cao, Jing
AU  - Shi, Mengyue
AU  - Schuck, Kathleen
AU  - Shi, Zhao
AU  - Zhang, Lingling
AU  - Li, Hongzhen
AU  - Sun, Yifeng
AU  - Fang, Chao
AU  - Hu, Jingxiong
AU  - Niu, Yiqi
AU  - Yu, Yuanyuan
AU  - Zhang, Zhiheng
AU  - Li, Chao
AU  - Hu, Mingyue
AU  - Wang, Lei
AU  - Jiang, Kuirong
AU  - Lu, Zipeng
AU  - Akkan, Jan
AU  - Raulefs, Susanne
AU  - Kahlert, Christoph
AU  - Roth, Susanne
AU  - Herr, Ingrid
AU  - Wan, Yuan
AU  - Mihaljevic, Andre
AU  - Qian, Xuetian
AU  - Zhang, Qi
AU  - Wang, Maggie Haitian
AU  - Kleeff, Jörg
AU  - Friess, Helmut
AU  - Gu, Zuguang
AU  - Michalski, Christoph W
AU  - Shen, Shanshan
AU  - Kong, Bo
TI  - ALDH1A3 promotes aggressive basal-like pancreatic cancer through an AP-1/RUNX2 enhancer network.
JO  - Oncogene
VL  - nn
SN  - 0950-9232
CY  - London
PB  - Springer Nature
M1  - DKFZ-2025-01662
SP  - nn
PY  - 2025
N1  - epub
AB  - 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.
LB  - PUB:(DE-HGF)16
C6  - pmid:40781158
DO  - DOI:10.1038/s41388-025-03530-w
UR  - https://inrepo02.dkfz.de/record/303449
ER  -