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| 001 | 303449 | ||
| 005 | 20250817022056.0 | ||
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| 082 | _ | _ | |a 610 |
| 100 | 1 | _ | |a Zou, Xiaoping |0 0000-0003-4147-7051 |b 0 |
| 245 | _ | _ | |a ALDH1A3 promotes aggressive basal-like pancreatic cancer through an AP-1/RUNX2 enhancer network. |
| 260 | _ | _ | |a London |c 2025 |b Springer Nature |
| 336 | 7 | _ | |a article |2 DRIVER |
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| 500 | _ | _ | |a epub |
| 520 | _ | _ | |a 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. |
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| 700 | 1 | _ | |a Nie, Shuang |b 1 |
| 700 | 1 | _ | |a Cao, Jing |b 2 |
| 700 | 1 | _ | |a Shi, Mengyue |b 3 |
| 700 | 1 | _ | |a Schuck, Kathleen |b 4 |
| 700 | 1 | _ | |a Shi, Zhao |b 5 |
| 700 | 1 | _ | |a Zhang, Lingling |b 6 |
| 700 | 1 | _ | |a Li, Hongzhen |b 7 |
| 700 | 1 | _ | |a Sun, Yifeng |b 8 |
| 700 | 1 | _ | |a Fang, Chao |b 9 |
| 700 | 1 | _ | |a Hu, Jingxiong |b 10 |
| 700 | 1 | _ | |a Niu, Yiqi |b 11 |
| 700 | 1 | _ | |a Yu, Yuanyuan |b 12 |
| 700 | 1 | _ | |a Zhang, Zhiheng |b 13 |
| 700 | 1 | _ | |a Li, Chao |b 14 |
| 700 | 1 | _ | |a Hu, Mingyue |b 15 |
| 700 | 1 | _ | |a Wang, Lei |b 16 |
| 700 | 1 | _ | |a Jiang, Kuirong |0 0000-0002-2849-5450 |b 17 |
| 700 | 1 | _ | |a Lu, Zipeng |b 18 |
| 700 | 1 | _ | |a Akkan, Jan |b 19 |
| 700 | 1 | _ | |a Raulefs, Susanne |b 20 |
| 700 | 1 | _ | |a Kahlert, Christoph |b 21 |
| 700 | 1 | _ | |a Roth, Susanne |b 22 |
| 700 | 1 | _ | |a Herr, Ingrid |b 23 |
| 700 | 1 | _ | |a Wan, Yuan |b 24 |
| 700 | 1 | _ | |a Mihaljevic, Andre |b 25 |
| 700 | 1 | _ | |a Qian, Xuetian |b 26 |
| 700 | 1 | _ | |a Zhang, Qi |b 27 |
| 700 | 1 | _ | |a Wang, Maggie Haitian |0 0000-0003-1223-4595 |b 28 |
| 700 | 1 | _ | |a Kleeff, Jörg |b 29 |
| 700 | 1 | _ | |a Friess, Helmut |b 30 |
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| 700 | 1 | _ | |a Michalski, Christoph W |b 32 |
| 700 | 1 | _ | |a Shen, Shanshan |0 0009-0000-7889-5674 |b 33 |
| 700 | 1 | _ | |a Kong, Bo |0 0009-0007-4997-8009 |b 34 |
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