Evidence map›Paper›PMID 37212485›Full record

ArticleCancer medicine2023

MiR-503 pleiotropically regulates epithelial-mesenchymal transition and targets PTK7 to control lung cancer metastasis.

Tzu-Hsiu Tsai, Chien-Hung Gow, Yi-Nan Liu, Meng-Feng Tsai, Tzu-Hua Chang, Shang-Gin Wu, Min-Shu Hsieh, Kang-Yi Su, Jin-Yuan Shih

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cancer medicine, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
1.7field-weighted citation impact, top 15% 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

6 citing papers in PubMed, 7 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 4 institutions in 1 country.

Tzu-Hsiu TsaiDepartment of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.ORCID 0000-0001-7532-2264
Chien-Hung GowDepartment of Internal Medicine, Far Eastern Memorial Hospital, New Taipei City, Taiwan.ORCID 0000-0001-6104-3459
Yi-Nan LiuDepartment of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.
Meng-Feng TsaiDepartment of Biomedical Sciences, Da-Yeh University, Changhua, Taiwan.
Tzu-Hua ChangDepartment of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.
Shang-Gin WuDepartment of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.ORCID 0000-0001-8889-689X
Min-Shu HsiehDepartment of Pathology, National Taiwan University Hospital, Taipei, Taiwan.
Kang-Yi SuDepartment of Clinical Laboratory Sciences and Medical Biotechnology College of Medicine, National Taiwan University, Taipei, Taiwan.
Jin-Yuan ShihDepartment of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.
National Taiwan University Hospital · TWNational Taiwan University · TWDayeh University · TWMing Chuan University · TW

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

objectiveIn lung cancer patients, most deaths are caused by the distant dissemination of cancer cells. Epithelial-mesenchymal transition (EMT) and collective cell migration are distinct and important mechanisms involved in cancer invasion and metastasis. Additionally, microRNA dysregulation contributes significantly to cancer progression. In this study, we aimed to explore the function of miR-503 in cancer metastasis.

methodsMolecular manipulations (silencing or overexpression) were performed to investigate the biological functions of miR-503 including migration and invasion. Reorganization of cytoskeleton was assessed using immunofluorescence and the relationship between miR-503 and downstream protein tyrosine kinase 7 (PTK7) was assessed using quantitative real-time PCR, immunoblotting, and reporter assays. The tail vein metastatic animal experiments were performed.

resultsHerein, we demonstrated that the downregulation of miR-503 confers an invasive phenotype in lung cancer cells and provided in vivo evidence that miR-503 significantly inhibits metastasis. We found that miR-503 inversely regulates EMT, identified PTK7 as a novel miR-503 target, and showed the functional effects of miR-503 on cell migration and invasion were restored upon reconstitution of PTK7 expression. As PTK7 is a Wnt/planar cell polarity protein crucial for collective cell movement, these results implicated miR-503 in both EMT and collective migration. However, the expression of PTK7 did not influence EMT induction, suggesting that miR-503 regulates EMT through mechanisms other than PTK7 inhibition. Furthermore, we discovered that PTK7 mechanistically activates focal adhesion kinase (FAK) and paxillin, thereby controlling the reorganization of the cortical actin cytoskeleton.

conclusionCollectively, miR-503 is capable of governing EMT and PTK7/FAK signaling independently to control the invasion and dissemination of lung cancer cells, indicating that miR-503 represents a pleiotropic regulator of cancer metastasis and hence a potential therapeutic target for lung cancer.

Indexed as

Lung NeoplasmsMicroRNAsAnimalsCell Line, TumorCell MovementEpithelial-Mesenchymal TransitionFocal Adhesion Protein-Tyrosine KinasesGene Expression Regulation, NeoplasticNeoplasm InvasivenessNeoplasm MetastasisSignal TransductionFocal Adhesion Protein-Tyrosine KinasesMicroRNAsactin cytoskeletonepithelial-mesenchymal transitionfocal adhesion kinasemiR-503protein tyrosine kinase 7

Identifiers

PMID37212485
PMCPMC10358207
OpenAlexW4377220884

What Socratic holds

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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.