ArticlePloS one2014
A high-content, multiplexed screen in human breast cancer cells identifies profilin-1 inducers with anti-migratory activities.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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The trial behind it
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Who cites it
10 citing papers in PubMed, 22 citations in OpenAlex.
- Tyrphostin A9 attenuates glioblastoma growth by suppressing PYK2/EGFR-ERK signaling pathway.Journal of neuro-oncology · 2023Article
- A High-Content Screening Assay for Small Molecules That Stabilize Mutant Triose Phosphate Isomerase (TPI) as Treatments for TPI Deficiency.SLAS discovery : advancing life sciences R & D · 2021Article
- Profilin: many facets of a small protein.Biophysical reviews · 2020Review
- Profilin choreographs actin and microtubules in cells and cancer.International review of cell and molecular biology · 2020Article
- Forecast of actin-binding proteins as the oncotarget in osteosarcoma - a review of mechanism, diagnosis and therapy.OncoTargets and therapy · 2018Review
- Global treadmilling coordinates actin turnover and controls the size of actin networks.Nature reviews. Molecular cell biology · 2017Review
- High content analysis in amyotrophic lateral sclerosis.Molecular and cellular neurosciences · 2017Review
- Profilin Interaction with Actin Filament Barbed End Controls Dynamic Instability, Capping, Branching, and Motility.Developmental cell · 2016Article
- Discovery of a Series of Acridinones as Mechanism-Based Tubulin Assembly Inhibitors with Anticancer Activity.PloS one · 2016Article
- Review
Corrections and comments
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Authors and funding
8 authors at 4 institutions in 1 country.
Funding
Abstract
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.
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Registered trials
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.