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The triple\u2010negative breast cancers (TNBCs) are characterized by malignant phenotypes, worse patient outcomes, poorest prognosis, and highest mortality rates. The proto\u2010oncogenic receptor tyrosine kinase c\u2010Met is usually dysregulated in TNBCs, contributing to their oncogenesis, tumor progression, and aggressive cellular invasiveness that is strongly linked to tumor metastasis. Therefore, c\u2010Met is proposed as a promising candidate target for the control of TNBCs. Lichens\u2010derived metabolites are characterized by their structural diversity, complexity, and novelty. The chemical space of lichen\u2010derived metabolites has been extensively investigated, albeit their biological space is still not fully explored. The anticancer\u2010guided fractionation of <jats:italic>Usnea strigosa<\/jats:italic> (Ach.) lichen extract led to the identification of the depsidone\u2010derived norstictic acid as a novel bioactive hit against breast cancer cell lines. Norstictic acid significantly suppressed the TNBC MDA\u2010MB\u2010231 cell proliferation, migration, and invasion, with minimal toxicity to non\u2010tumorigenic MCF\u201010A mammary epithelial cells. Molecular modeling, Z'\u2010LYTE biochemical kinase assay and Western blot analysis identified c\u2010Met as a potential macromolecular target. Norstictic acid treatment significantly suppressed MDA\u2010MB\u2010231\/GFP tumor growth of a breast cancer xenograft model in athymic nude mice. Lichen\u2010derived natural products are promising resources to discover novel c\u2010Met inhibitors useful to control TNBCs. Copyright \u00a9 2016 John Wiley &amp; Sons, Ltd.<\/jats:p>","DOI":"10.1002\/ptr.5551","type":"journal-article","created":{"date-parts":[[2016,1,8]],"date-time":"2016-01-08T05:34:14Z","timestamp":1452231254000},"page":"557-566","source":"Crossref","is-referenced-by-count":60,"title":["Norstictic Acid Inhibits Breast Cancer Cell Proliferation, Migration, Invasion, and <i>In Vivo<\/i> Invasive Growth Through Targeting C\u2010Met"],"prefix":"10.1002","volume":"30","author":[{"given":"Hassan Y.","family":"Ebrahim","sequence":"first","affiliation":[{"name":"Department of Basic Pharmaceutical Sciences, School of Pharmacy University of Louisiana at Monroe  Monroe Louisiana 71201 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heba E.","family":"Elsayed","sequence":"additional","affiliation":[{"name":"Department of Basic Pharmaceutical Sciences, School of Pharmacy University of Louisiana at Monroe  Monroe Louisiana 71201 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