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Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2023,11,21]]},"abstract":"<jats:p>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.<\/jats:p>","DOI":"10.1073\/pnas.2303978120","type":"journal-article","created":{"date-parts":[[2023,11,14]],"date-time":"2023-11-14T14:59:46Z","timestamp":1699973986000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":6,"title":["Invasion-Block and S-MARVEL: A high-content screening and image analysis platform identifies ATM kinase as a modulator of melanoma invasion and metastasis"],"prefix":"10.1073","volume":"120","author":[{"given":"Dajiang","family":"Guo","sequence":"first","affiliation":[{"name":"Immune Imaging Program, Centenary Institute, Faculty of Medicine and Health, The University of Sydney, Camperdown, NSW 2050, Australia"},{"name":"Sydney Medical School, The University of Sydney, Camperdown, NSW 2050, 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