Evidence map›Paper›PMID 39738173›Full record

ArticleScientific reports2024

Hypoxia drives the formation of lung micropapillary adenocarcinoma-like structure through hypoxia-inducible factor-1α.

Daisuke Umeda, Akikazu Harada, Daisuke Motooka, Shinichiro Tahara, Masako Kurashige, Kansuke Kido, Tsuyoshi Takashima, Hiroki Kiyokawa, Koto Ukon, Takahiro Matsui and 6 more

Abstract read
In one paragraph

Article in Scientific reports, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing 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

2 citing papers in PubMed.

  1. Biomimetic Scaffold-Based 3D Models for Decoding Cancer Biology and Advancing Therapy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026
    Review
  2. Article
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.

Daisuke UmedaDepartment of Pathology, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan.
Akikazu HaradaDepartment of Molecular Biology and Biochemistry, Graduate School of Medicine, Osaka University, Suita, Japan.
Daisuke MotookaIntegrated Frontier Research for Medical Science Division, Institute for Open and Transdisciplinary Research Initiatives (OTRI), Osaka University Institute for Open and Transdisciplinary Research Initiatives, Osaka University, Osaka, Japan.
Shinichiro TaharaDepartment of Pathology, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan.
Masako KurashigeDepartment of Pathology, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan.
Kansuke KidoDepartment of Pathology, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan.
Tsuyoshi TakashimaDepartment of Pathology, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan.
Hiroki KiyokawaDepartment of Pathology, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan.
Koto UkonDepartment of Pathology, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan.
Takahiro MatsuiDepartment of Pathology, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan.
Shinji MatsumotoDepartment of Molecular Biology and Biochemistry, Graduate School of Medicine, Osaka University, Suita, Japan.
Yasushi ShintaniDepartment of General Thoracic Surgery, Osaka University Graduate School of Medicine, Osaka, Japan.
Daisuke OkuzakiIntegrated Frontier Research for Medical Science Division, Institute for Open and Transdisciplinary Research Initiatives (OTRI), Osaka University Institute for Open and Transdisciplinary Research Initiatives, Osaka University, Osaka, Japan.
Akira KikuchiCenter for Infectious Disease Education and Research, Osaka University, Osaka, Japan.
Satoshi NojimaDepartment of Pathology, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan. s_nojima@molpath.med.osaka-u.ac.jp.
Eiichi MoriiDepartment of Pathology, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan. morii@molpath.med.osaka-u.ac.jp.

Funding

Japan Agency for Medical Research and Development (AMED) JP21ae0121049Japan Society for the Promotion of Science (JSPS) KAKENHI A19H034520Japan Society for the Promotion of Science (JSPS) KAKENHI T21K069030Japan Society for the Promotion of Science (JSPS) KAKENHI T21K070980
6 · The paper itself

Abstract

Micropapillary adenocarcinoma (MPC) is an aggressive histological subtype of lung adenocarcinoma (LUAD). MPC is composed of small clusters of cancer cells exhibiting inverted polarity. However, the mechanism underlying its formation is poorly understood. Here we show that hypoxia is involved in MPC formation. Hypoxia induced the formation of MPC-like structures (MLSs) in a three-dimensional culture system using A549 human LUAD cells, and HIF-1α was indispensable for MLS formation. RNA sequencing analysis demonstrated that A549 cells forming MLSs exhibited a gene expression signature similar to that of lung MPC. Moreover, MLS formation enhanced the resistance of A549 cells to natural killer cell cytotoxicity. Our findings suggest that hypoxia drives lung MPC formation through HIF-1α and that immune escape from natural killer cells might underlie the aggressiveness of MPC.

Indexed as

Adenocarcinoma of LungHypoxia-Inducible Factor 1, alpha SubunitLung NeoplasmsA549 CellsAdenocarcinoma, PapillaryCell HypoxiaCell Line, TumorGene Expression Regulation, NeoplasticHumansHypoxiaKiller Cells, NaturalHIF1A protein, humanHypoxia-Inducible Factor 1, alpha SubunitHypoxiaHypoxia-inducible factor-1αLung micropapillary adenocarcinomaMatrigelMUC1Natural killer cell cytotoxicityRhoRho-kinaseThree-dimensional cell culture

Identifiers

PMID39738173
PMCPMC11685966

What OpenQuestion holds

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Registered trials

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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 OpenQuestion graph.