Evidence map›Paper›PMID 34638565›Full record

ArticleInternational journal of molecular sciences2021

The Role of E-Cadherin and microRNA on FAK Inhibitor Response in Malignant Pleural Mesothelioma (MPM).

Man Lee Yuen, Ling Zhuang, Emma M Rath, Takun Yu, Ben Johnson, Kadir Harun Sarun, Yiwei Wang, Steven Kao, Anthony Linton, Candice Julie Clarke and 4 more

Open access · goldAbstract read
In one paragraph

Article in International journal of molecular sciences, 2021. 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
0.6field-weighted citation impact, top 30% 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.

  1. Article
  2. Review
  3. Article
  4. Review
  5. Article
  6. 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

14 authors at 5 institutions in 2 countries.

Man Lee YuenAsbestos Diseases Research Institute, Sydney, NSW 2139, Australia.
Ling ZhuangAsbestos Diseases Research Institute, Sydney, NSW 2139, Australia.
Emma M RathVictor Chang Cardiac Research Institute, Darlinghurst, NSW 2010, Australia.ORCID 0000-0002-8430-5236
Takun YuAsbestos Diseases Research Institute, Sydney, NSW 2139, Australia.
Ben JohnsonAsbestos Diseases Research Institute, Sydney, NSW 2139, Australia.
Kadir Harun SarunAsbestos Diseases Research Institute, Sydney, NSW 2139, Australia.
Yiwei WangJiangsu Provincial Engineering Research Centre of TCM External Medication Development and Application, Nanjing University of Chinese Medicine, Nanjing 210023, China.
Steven KaoAsbestos Diseases Research Institute, Sydney, NSW 2139, Australia.
Anthony LintonAsbestos Diseases Research Institute, Sydney, NSW 2139, Australia.
Candice Julie ClarkeAnatomical Pathology Department, NSW Health Pathology, Concord Repatriation General Hospital, Concord, NSW 2139, Australia.
Brian C McCaughanSydney Cardiothoracic Surgeons, RPA Medical Centre, Sydney, NSW 2042, Australia.
Ken TakahashiAsbestos Diseases Research Institute, Sydney, NSW 2139, Australia.
Kenneth LeeAsbestos Diseases Research Institute, Sydney, NSW 2139, Australia.
Yuen Yee ChengAsbestos Diseases Research Institute, Sydney, NSW 2139, Australia.
Asbestos Diseases Research Institute · AUThe University of Sydney · AUConcord Repatriation General Hospital · AUNew South Wales Department of Health · AUVictor Chang Cardiac Research Institute · AU

Funding

Regional Collaboration Program Grant 2018
6 · The paper itself

Abstract

Malignant pleural mesothelioma (MPM) is an aggressive malignancy with limited effective treatment options. Focal adhesion kinase (FAK) inhibitors have been shown to efficiently suppress MPM cell growth initially, with limited utility in the current clinical setting. In this study, we utilised a large collection of MPM cell lines and MPM tissue samples to study the role of E-cadherin (CDH1) and microRNA on the efficacy of FAK inhibitors in MPM. The immunohistochemistry (IHC) results showed that the majority of MPM FFPE samples exhibited either the absence of, or very low, E-cadherin protein expression in MPM tissue. We showed that MPM cells with high CDH1 mRNA levels exhibited resistance to the FAK inhibitor PND-1186. In summary, MPM cells that did not express CDH1 mRNA were sensitive to PND-1186, and MPM cells that retained CDH1 mRNA were resistant. A cell cycle analysis showed that PND-1186 induced cell cycle disruption by inducing the G2/M arrest of MPM cells. A protein-protein interaction study showed that EGFR is linked to the FAK pathway, and a target scan of the microRNAs revealed that microRNAs (miR-17, miR221, miR-222, miR137, and miR148) interact with EGFR 3'UTR. Transfection of MPM cells with these microRNAs sensitised the CHD1-expressing FAK-inhibitor-resistant MPM cells to the FAK inhibitor.

Indexed as

AminopyridinesAntigens, CDCadherinsCell CycleCell Line, TumorErbB ReceptorsFocal Adhesion Kinase 1HumansMesothelioma, MalignantMicroRNAsProtein Interaction MapsProtein Kinase InhibitorsAminopyridinesAntigens, CDCadherinsCDH1 protein, humanEGFR protein, humanErbB ReceptorsFocal Adhesion Kinase 1MicroRNAsMIR221, humanMIR222, humanMIRN137 microRNA, humanMIRN148 microRNA, humanMIRN17 microRNA, humanPND 1186Protein Kinase InhibitorsPTK2 protein, humandrug resistantE-cadherinFAK inhibitormalignant pleural mesothelioma (MPM)microRNA

Identifiers

PMID34638565
PMCPMC8508233
OpenAlexW3199756945

What OpenQuestion holds

Textmetadata
LicenceCC BY
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 OpenQuestion graph.