Evidence mapPaperPMID 37094129Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2023

Hypoxia induces downregulation of the tumor-suppressive sST2 in colorectal cancer cells via the HIF-nuclear IL-33-GATA3 pathway.

Miho Akimoto, Takao Susa, Noriyuki Okudaira, Nobuko Koshikawa, Harumi Hisaki, Masayoshi Iizuka, Hiroko Okinaga, Keizo Takenaga, Tomoki Okazaki, Mimi Tamamori-Adachi

Open access · greenAbstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed
1.6field-weighted citation impact, top 16% of its field
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

8 citing papers in PubMed, 10 citations in OpenAlex.

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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

10 authors at 2 institutions in 1 country.

Miho AkimotoDepartment of Biochemistry, Teikyo University School of Medicine, Kaga, Itabashi-ku, Tokyo 173-8605, Japan.ORCID 0000-0003-1774-2257
Takao SusaDepartment of Biochemistry, Teikyo University School of Medicine, Kaga, Itabashi-ku, Tokyo 173-8605, Japan.
Noriyuki OkudairaDepartment of Biochemistry, Teikyo University School of Medicine, Kaga, Itabashi-ku, Tokyo 173-8605, Japan.
Nobuko KoshikawaDepartment of Innovative Cancer Therapeutics, Chiba Cancer Center Research Institute, Nitona, Chuoh-ku, Chiba 260-8717, Japan.ORCID 0000-0003-1468-563X
Harumi HisakiDepartment of Biochemistry, Teikyo University School of Medicine, Kaga, Itabashi-ku, Tokyo 173-8605, Japan.
Masayoshi IizukaDepartment of Biochemistry, Teikyo University School of Medicine, Kaga, Itabashi-ku, Tokyo 173-8605, Japan.
Hiroko OkinagaDepartment of Internal Medicine, Teikyo University School of Medicine, Kaga, Itabashi-ku, Tokyo 173-8605, Japan.
Keizo TakenagaDepartment of Innovative Cancer Therapeutics, Chiba Cancer Center Research Institute, Nitona, Chuoh-ku, Chiba 260-8717, Japan.ORCID 0000-0002-5341-6742
Tomoki OkazakiDepartment of Biochemistry, Teikyo University School of Medicine, Kaga, Itabashi-ku, Tokyo 173-8605, Japan.
Mimi Tamamori-AdachiDepartment of Biochemistry, Teikyo University School of Medicine, Kaga, Itabashi-ku, Tokyo 173-8605, Japan.
Teikyo University · JPChiba Cancer Center · JP

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

As a decoy receptor, soluble ST2 (sST2) interferes with the function of the inflammatory cytokine interleukin (IL)-33. Decreased sST2 expression in colorectal cancer (CRC) cells promotes tumor growth via IL-33-mediated bioprocesses in the tumor microenvironment. In this study, we discovered that hypoxia reduced sST2 expression in CRC cells and explored the associated molecular mechanisms, including the expression of key regulators of ST2 gene transcription in hypoxic CRC cells. In addition, the effect of the recovery of sST2 expression in hypoxic tumor regions on malignant progression was investigated using mouse CRC cells engineered to express sST2 in response to hypoxia. Our results indicated that hypoxia-dependent increases in nuclear IL-33 interfered with the transactivation activity of GATA3 for ST2 gene transcription. Most importantly, hypoxia-responsive sST2 restoration in hypoxic tumor regions corrected the inflammatory microenvironment and suppressed tumor growth and lung metastasis. These results indicate that strategies targeting sST2 in hypoxic tumor regions could be effective for treating malignant CRC.

Indexed as

Colorectal NeoplasmsInterleukin-33AnimalsCell NucleusDown-RegulationGATA3 Transcription FactorInterleukin-1 Receptor-Like 1 ProteinMiceTumor MicroenvironmentGata3 protein, mouseGATA3 Transcription FactorInterleukin-1 Receptor-Like 1 ProteinInterleukin-33colorectal cancerhypoxiainterleukin-33metastasissoluble ST2

Identifiers

PMID37094129
PMCPMC10160999
OpenAlexW4366816366

What Socratic 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 Socratic graph.