Evidence map›Paper›PMID 35563439›Full record

ArticleInternational journal of molecular sciences2022

Novel Inhibitor for Downstream Targeting of Transforming Growth Factor-β Signaling to Suppress Epithelial to Mesenchymal Transition and Cell Migration.

Tsugumasa Toma, Hiroshi Tateishi, Kensaku Kawakami, Taha F S Ali, Masahiro Kamo, Kazuaki Monde, Yuta Nakashima, Mikako Fujita, Masami Otsuka

Open access · goldAbstract read
In one paragraph

Article in International journal of molecular sciences, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
0.9field-weighted citation impact, top 29% 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

4 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

9 authors at 3 institutions in 2 countries.

Tsugumasa TomaMedicinal and Biological Chemistry Science Farm Joint Research Laboratory, Faculty of Life Sciences, Kumamoto University, Kumamoto 862-0973, Japan.
Hiroshi TateishiMedicinal and Biological Chemistry Science Farm Joint Research Laboratory, Faculty of Life Sciences, Kumamoto University, Kumamoto 862-0973, Japan.ORCID 0000-0003-1225-0720
Kensaku KawakamiGraduate School of Science and Technology, Kumamoto University, Kumamoto 860-8555, Japan.
Taha F S AliMedicinal and Biological Chemistry Science Farm Joint Research Laboratory, Faculty of Life Sciences, Kumamoto University, Kumamoto 862-0973, Japan.ORCID 0000-0002-8881-0408
Masahiro KamoMedicinal and Biological Chemistry Science Farm Joint Research Laboratory, Faculty of Life Sciences, Kumamoto University, Kumamoto 862-0973, Japan.
Kazuaki MondeDepartment of Microbiology, Faculty of Life Sciences, Kumamoto University, Kumamoto 860-8556, Japan.
Yuta NakashimaFaculty of Advanced Science and Technology, Kumamoto University, Kumamoto 860-8555, Japan.ORCID 0000-0003-3151-4963
Mikako FujitaMedicinal and Biological Chemistry Science Farm Joint Research Laboratory, Faculty of Life Sciences, Kumamoto University, Kumamoto 862-0973, Japan.ORCID 0000-0001-6705-4052
Masami OtsukaMedicinal and Biological Chemistry Science Farm Joint Research Laboratory, Faculty of Life Sciences, Kumamoto University, Kumamoto 862-0973, Japan.
Kumamoto University · JPKumamoto Industrial Research Institute · JPMinia University · EG

Funding

Japan Society for the Promotion of Science 17H03999
6 · The paper itself

Abstract

Cancer metastasis accounts for most of the mortality associated with solid tumors. However, antimetastatic drugs are not available on the market. One of the important biological events leading to metastasis is the epithelial to mesenchymal transition (EMT) induced by cytokines, namely transforming growth-factor-β (TGF-β). Although several classes of inhibitors targeting TGF-β and its receptor have been developed, they have shown profound clinical side effects. We focused on our synthetic compound, HPH-15, which has shown anti-fibrotic activity via the blockade of the TGF-β Smad-dependent signaling. In this study, 10 μM of HPH-15 was found to exhibit anti-cell migration and anti-EMT activities in non-small-cell lung cancer (NSCLC) cells. Although higher concentrations are required, the anti-EMT activity of HPH-15 has also been observed in 3D-cultured NSCLC cells. A mechanistic study showed that HPH-15 inhibits downstream TGF-β signaling. This downstream inhibition blocks the expression of cytokines such as TGF-β, leading to the next cycle of Smad-dependent and -independent signaling. HPH-15 has AMPK-activation activity, but a relationship between AMPK activation and anti-EMT/cell migration was not observed. Taken together, HPH-15 may lead to the development of antimetastatic drugs with a new mechanism of action.

Indexed as

Carcinoma, Non-Small-Cell LungEpithelial-Mesenchymal TransitionSignal TransductionTransforming Growth Factor betaAMP-Activated Protein KinasesCell Line, TumorCell MovementHumansLung NeoplasmsTransforming Growth Factor beta1Transforming Growth FactorsAMP-Activated Protein KinasesTransforming Growth Factor betaTransforming Growth Factor beta1Transforming Growth Factorsanti-cell migrationanti-epithelial to mesenchymal transition (EMT)non-small-cell lung cancer (NSCLC) cellsSmadtransforming growth factor-β (TGF-β)

Identifiers

PMID35563439
PMCPMC9102712
OpenAlexW4225286503

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.