Evidence mapPaperPMID 42234404Full record

ArticleAdvanced science (Weinheim, Baden-Wurttemberg, Germany)2026

PDIA6-SCD1 Axis Rewires Lipid Metabolism to Drive Gastric Cancer Progression.

Zhen Tian, Yifan Cheng, Jiajie Zhou, Ruiqi Li, Shuai Zhao, Ben Li, Zijie Xu, Mengli Zi, Yayan Fu, Chenkai Zhang and 4 more

Abstract read
In one paragraph

Article in Advanced science (Weinheim, Baden-Wurttemberg, Germany), 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

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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

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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

14 authors.

Zhen TianNorthern Jiangsu People's Hospital, Clinical Teaching Hospital of Medical School, Nanjing University, Yangzhou, China.ORCID https://orcid.org/0000-0002-3759-6368
Yifan ChengNorthern Jiangsu People's Hospital, Clinical Teaching Hospital of Medical School, Nanjing University, Yangzhou, China.
Jiajie ZhouNorthern Jiangsu People's Hospital, Clinical Teaching Hospital of Medical School, Nanjing University, Yangzhou, China.
Ruiqi LiNorthern Jiangsu People's Hospital, Clinical Teaching Hospital of Medical School, Nanjing University, Yangzhou, China.ORCID https://orcid.org/0000-0002-1057-3166
Shuai ZhaoNorthern Jiangsu People's Hospital, Clinical Teaching Hospital of Medical School, Nanjing University, Yangzhou, China.
Ben LiNorthern Jiangsu People's Hospital, Clinical Teaching Hospital of Medical School, Nanjing University, Yangzhou, China.ORCID https://orcid.org/0000-0002-3417-0521
Zijie XuNorthern Jiangsu People's Hospital, Clinical Teaching Hospital of Medical School, Nanjing University, Yangzhou, China.
Mengli ZiNorthern Jiangsu People's Hospital, Clinical Teaching Hospital of Medical School, Nanjing University, Yangzhou, China.
Yayan FuNorthern Jiangsu People's Hospital Affiliated to Yangzhou University, Yangzhou, China.ORCID https://orcid.org/0000-0001-5523-3424
Chenkai ZhangNorthern Jiangsu People's Hospital Affiliated to Yangzhou University, Yangzhou, China.
Qiannan SunYangzhou Key Laboratory Of Basic And Clinical Transformation of Digestive And Metabolic Diseases, Yangzhou, China.
Shantanu BaralDepartment of General Surgery, Northern Jiangsu People's Hospital, Yangzhou, China.
Sen WangDepartment of General Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
Daorong WangNorthern Jiangsu People's Hospital, Clinical Teaching Hospital of Medical School, Nanjing University, Yangzhou, China.ORCID https://orcid.org/0000-0003-1642-0889

Funding

National Natural Science Foundation of China NO. 82373014
6 · The paper itself

Abstract

Gastric cancer (GC) remains an aggressive malignancy with limited effective therapeutic options. Integrated single-cell and bulk transcriptomic analyses identify protein disulfide isomerase A6 (PDIA6) as a tumor epithelial-enriched gene associated with advanced tumor‑ node‑metastasis (TNM) stage and unfavorable survival. Multi-omics profiling reveals that PDIA6 drives lipid metabolic reprogramming by sustaining the monounsaturated fatty acid (MUFA)-enriched neutral lipid pools required for lipid droplet homeostasis and redox balance. Mechanistically, PDIA6 directly associates with stearoyl-CoA desaturase 1 (SCD1) through a structure-defined interface centered on Asp44 of SCD1, thereby restricting its ubiquitin-proteasome-mediated degradation and maintaining SCD1-dependent fatty acid desaturation. In vivo, PDIA6 knockdown suppresses tumor growth and liver metastasis, and synergistic SCD1 inhibition (CAY10566) yields efficacy superior to monotherapies. Upstream, tumor-stromal interactions may contribute to PDIA6 upregulation, as cancer-associated fibroblast-derived C-X-C motif chemokine ligand 12 (CXCL12) activated C-X-C chemokine receptor 4 (CXCR4)-dependent signal transducer and activator of transcription 3 (STAT3) signaling in vitro. These findings establish the PDIA6-SCD1 axis as a targetable lipid metabolic dependency in GC and position PDIA6 as a candidate therapeutic vulnerability for precision oncology.

Indexed as

cancer‐associated fibroblastsgastric cancerlipid metabolismprotein disulfide isomerase

Identifiers

PMID42234404
PMCPMC13336654

What Socratic holds

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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 Socratic graph.