Evidence map›Paper›PMID 42221815›Full record

ArticleiScience2026

ALDH1A3 promotes the lung metastatic organotropism of pancreatic ductal adenocarcinoma through semaphorin signaling.

Shanshan Shen, Xuetian Qian, Zhao Shi, Yuting Wu, Zitong Zhou, Shuang Nie, Yuanyuan Yu, Siqi Zhou, Kun Liu, Quan Zhou and 6 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in iScience, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

16 authors.

Shanshan ShenDepartment of Gastroenterology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China.
Xuetian QianDepartment of Gastroenterology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China.
Zhao ShiDepartment of Gastroenterology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China.
Yuting WuDepartment of Gastroenterology, Nanjing Drum Tower Hospital, Clinical College of Nanjing University of Chinese Medicine, Nanjing, China.
Zitong ZhouDepartment of Gastroenterology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China.
Shuang NieDepartment of Gastroenterology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China.
Yuanyuan YuDepartment of Gastroenterology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China.
Siqi ZhouDepartment of Gastroenterology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China.
Kun LiuDepartment of Gastroenterology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China.
Quan ZhouDepartment of Gastroenterology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China.
Dehua TangDepartment of Gastroenterology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China.
Ying LvDepartment of Gastroenterology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China.
Lei WangDepartment of Gastroenterology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China.
Bo KongDepartment of Gastroenterology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China.
Hongzhen LiDepartment of Gastroenterology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China.
Xiaoping ZouDepartment of Gastroenterology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignancy characterized by early metastasis and poor prognosis. Here, we demonstrate that aldehyde dehydrogenase 1A3 (ALDH1A3) regulates PDAC lung tropism through an epigenetic-axon guidance axis. RNA sequencing analysis of clinical samples revealed that PDAC lung recurrence is associated with basal-like features and involves retinol metabolism and axon guidance pathways. Mechanistically, ALDH1A3 promotes acetyl-CoA production, enhancing histone H3 (H3K9/K14) acetylation at promoters of axon guidance receptors PLXNB1 and NRP1 to activate their transcription. Consequently, PDAC cells become sensitized to ligands SEMA4D and SEMA3A, which are abundantly expressed in lung epithelial cells. The resulting SEMA4D-PLXNB1 and SEMA3A-NRP1 signaling axes drive early metastatic colonization in the lung. Our findings reveal a regulatory circuit underlying PDAC organotropism and suggest potential therapeutic strategies against metastasis.

Indexed as

Biological sciencesMicroenvironment

Identifiers

PMID42221815
PMCPMC13217847

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.