<> "The repository administrator has not yet configured an RDF license."^^ . <> . . . "A high-content, multiplexed screen in human breast cancer cells identifies profilin-1 inducers with anti-migratory activities"^^ . "Profilin-1 (Pfn-1) is a ubiquitously expressed actin-binding protein that is essential for normal cell proliferation and migration. In breast cancer and several other adenocarcinomas, Pfn-1 expression is downregulated when compared to normal tissues. Previous studies from our laboratory have shown that genetically modulating Pfn-1 expression significantly impacts proliferation, migration, and invasion of breast cancer cells in vitro, and mammary tumor growth, dissemination, and metastatic colonization in vivo. Therefore, small molecules that can modulate Pfn-1 expression could have therapeutic potential in the treatment of metastatic breast cancer. The overall goal of this study was to perform a multiplexed phenotypic screen to identify compounds that inhibit cell motility through upregulation of Pfn-1. Screening of a test cassette of 1280 compounds with known biological activities on an Oris™ Pro 384 cell migration platform identified several agents that increased Pfn-1 expression greater than two-fold over vehicle controls and exerted anti-migratory effects in the absence of overt cytotoxicity in MDA-MB-231 human breast cancer cells. Concentration-response confirmation and orthogonal follow-up assays identified two bona fide inducers of Pfn-1, purvalanol and tyrphostin A9, that confirmed in single-cell motility assays and Western blot analyses. SiRNA-mediated knockdown of Pfn-1 abrogated the inhibitory effect of tyrphostin A9 on cell migration, suggesting Pfn-1 is mechanistically linked to tyrphostin A9's anti-migratory activity. The data illustrate the utility of the high-content cell motility assay to discover novel targeted anti-migratory agents by integrating functional phenotypic analyses with target-specific readouts in a single assay platform. © 2014 Joy et al."^^ . "2014-02-10" . . . "9" . "2" . . "PLoS ONE"^^ . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . "CK"^^ . "Peterson"^^ . "CK Peterson"^^ . . "P"^^ . "Roy"^^ . "P Roy"^^ . . "Alissa M."^^ . "Weaver"^^ . "Alissa M. Weaver"^^ . . "LL"^^ . "Vollmer"^^ . "LL Vollmer"^^ . . "K"^^ . "Hulkower"^^ . "K Hulkower"^^ . . "RC"^^ . "Boltz"^^ . "RC Boltz"^^ . . "A"^^ . "Vogt"^^ . "A Vogt"^^ . . "AM"^^ . "Stern"^^ . "AM Stern"^^ . . "ME"^^ . "Joy"^^ . "ME Joy"^^ . . . . . . "A high-content, multiplexed screen in human breast cancer cells identifies profilin-1 inducers with anti-migratory activities (PDF)"^^ . . . . . . . . "journal.pone.0088350.pdf"^^ . . . "A high-content, multiplexed screen in human breast cancer cells identifies profilin-1 inducers with anti-migratory activities (Indexer Terms)"^^ . . . . . . "indexcodes.txt"^^ . . . "A high-content, multiplexed screen in human breast cancer cells identifies profilin-1 inducers with anti-migratory activities (Other)"^^ . . . . . . "lightbox.jpg"^^ . . . "A high-content, multiplexed screen in human breast cancer cells identifies profilin-1 inducers with anti-migratory activities (Other)"^^ . . . . . . "preview.jpg"^^ . . . "A high-content, multiplexed screen in human breast cancer cells identifies profilin-1 inducers with anti-migratory activities (Other)"^^ . . . . . . "medium.jpg"^^ . . . "A high-content, multiplexed screen in human breast cancer cells identifies profilin-1 inducers with anti-migratory activities (Other)"^^ . . . . . . "small.jpg"^^ . . . "A high-content, multiplexed screen in human breast cancer cells identifies profilin-1 inducers with anti-migratory activities (Plain Text)"^^ . . . "licence.txt"^^ . . . "A high-content, multiplexed screen in human breast cancer cells identifies profilin-1 inducers with anti-migratory activities (Other)"^^ . . . . . . "indexcodes.txt"^^ . . "HTML Summary of #21905 \n\nA high-content, multiplexed screen in human breast cancer cells identifies profilin-1 inducers with anti-migratory activities\n\n" . "text/html" . .