Evidence map›Paper›PMID 37963252›Full record

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

Invasion-Block and S-MARVEL: A high-content screening and image analysis platform identifies ATM kinase as a modulator of melanoma invasion and metastasis.

Dajiang Guo, Russell Jurek, Kimberley A Beaumont, Danae S Sharp, Sioh-Yang Tan, Anna Mariana, Timothy W Failes, Abigail K Grootveld, Nayan D Bhattacharyya, Tri Giang Phan and 4 more

Open access · greenAbstract read
PubMed Full text at PMC Publisher
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 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 20% 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, 4 citations in OpenAlex.

  1. Review
  2. Review
  3. Review
  4. Review
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 4 institutions in 2 countries.

Dajiang Guo *Immune Imaging Program, Centenary Institute, Faculty of Medicine and Health, The University of Sydney, Camperdown, NSW 2050, Australia.
Russell Jurek *Australia Telescope National Facility, The Commonwealth Scientific and Industrial Research Organisation (CSIRO) Astronomy and Space Science, Australia Telescope National Facility, Marsfield NSW 2122, Australia.
Kimberley A BeaumontImmune Imaging Program, Centenary Institute, Faculty of Medicine and Health, The University of Sydney, Camperdown, NSW 2050, Australia.
Danae S SharpImmune Imaging Program, Centenary Institute, Faculty of Medicine and Health, The University of Sydney, Camperdown, NSW 2050, Australia.
Sioh-Yang TanImmune Imaging Program, Centenary Institute, Faculty of Medicine and Health, The University of Sydney, Camperdown, NSW 2050, Australia.
Anna MarianaThe Australian Cancer Research Foundation (ACRF) Drug Discovery Centre for Childhood Cancer, Children's Cancer Institute, Lowy Cancer Research Centre, University of New South Wales (UNSW) Sydney, Sydney, NSW 2052, Australia.
Timothy W FailesThe Australian Cancer Research Foundation (ACRF) Drug Discovery Centre for Childhood Cancer, Children's Cancer Institute, Lowy Cancer Research Centre, University of New South Wales (UNSW) Sydney, Sydney, NSW 2052, Australia.
Abigail K GrootveldGarvan Institute of Medical Research, Darlinghurst, Sydney, NSW 2010, Australia.
Nayan D BhattacharyyaGarvan Institute of Medical Research, Darlinghurst, Sydney, NSW 2010, Australia.
Tri Giang PhanGarvan Institute of Medical Research, Darlinghurst, Sydney, NSW 2010, Australia.
Greg M ArndtThe Australian Cancer Research Foundation (ACRF) Drug Discovery Centre for Childhood Cancer, Children's Cancer Institute, Lowy Cancer Research Centre, University of New South Wales (UNSW) Sydney, Sydney, NSW 2052, Australia.
Rohit Jain *Immune Imaging Program, Centenary Institute, Faculty of Medicine and Health, The University of Sydney, Camperdown, NSW 2050, Australia.
Wolfgang Weninger *Immune Imaging Program, Centenary Institute, Faculty of Medicine and Health, The University of Sydney, Camperdown, NSW 2050, Australia.
Shweta Tikoo *Immune Imaging Program, Centenary Institute, Faculty of Medicine and Health, The University of Sydney, Camperdown, NSW 2050, Australia.ORCID 0000-0001-5850-8075
The University of Sydney · AUAustralian Cancer Research Foundation · AUGarvan Institute of Medical Research · AUCommonwealth Scientific and Industrial Research Organisation · AU

Funding

DHAC | National Health and Medical Research Council (NHMRC) APP1155678Tour de Cure (TDC) 17CENI-RP-01
6 · The paper itself

Abstract

Robust high-throughput assays are crucial for the effective functioning of a drug discovery pipeline. Herein, we report the development of Invasion-Block, an automated high-content screening platform for measuring invadopodia-mediated matrix degradation as a readout for the invasive capacity of cancer cells. Combined with Smoothen-Mask and Reveal, a custom-designed, automated image analysis pipeline, this platform allowed us to evaluate melanoma cell invasion capacity posttreatment with two libraries of compounds comprising 3840 U.S. Food and Drug Administration (FDA)-approved drugs with well-characterized safety and bioavailability profiles in humans as well as a kinase inhibitor library comprising 210 biologically active compounds. We found that Abl/Src, PKC, PI3K, and Ataxia-telangiectasia mutated (ATM) kinase inhibitors significantly reduced melanoma cell invadopodia formation and cell invasion. Abrogation of ATM expression in melanoma cells via CRISPR-mediated gene knockout reduced 3D invasion in vitro as well as spontaneous lymph node metastasis in vivo. Together, this study established a rapid screening assay coupled with a customized image-analysis pipeline for the identification of antimetastatic drugs. Our study implicates that ATM may serve as a potent therapeutic target for the treatment of melanoma cell spread in patients.

Indexed as

Antineoplastic AgentsAtaxia TelangiectasiaMelanomaAtaxia Telangiectasia Mutated ProteinsCell Line, TumorHigh-Throughput Screening AssaysHumansAntineoplastic AgentsAtaxia Telangiectasia Mutated ProteinsATM protein, humanhigh-throughput screeningimagingmelanoma metastasis

Identifiers

PMID37963252
PMCPMC10666109
OpenAlexW4388665357

What OpenQuestion 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 OpenQuestion graph.