Abstract
Better understanding the mechanisms underlying the metastatic process is essential to developing novel targeted therapeutics. Recently, invadopodia have been increasingly recognized as important drivers of local invasion in metastasis. Invadopodia are basally-localized, actin-rich structures that concentrate protease activity to areas of the cell in contact with the extracellular matrix. We recently found that the transcription factor Twist1, a central regulator of the epithelial-mesenchymal transition (EMT), promotes invadopodia formation via upregulation of platelet-derived growth factor receptor (PDGFR) expression and activity. This finding, combined with other investigations into the mechanisms of invadopodia formation, reveal several novel targets for clinical inhibition of invadopodia. Here, we provide an overview of clinically-relevant targets for intervention in invadopodia, including Src signaling, PDGFR signaling, and metalloprotease activity.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, Non-P.H.S.
MeSH terms
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Actins / metabolism
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Animals
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Breast Neoplasms / drug therapy*
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Breast Neoplasms / metabolism
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Breast Neoplasms / pathology*
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Cell Line, Tumor
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Cell Surface Extensions / drug effects*
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Cell Surface Extensions / ultrastructure
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Epithelial-Mesenchymal Transition / drug effects
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Epithelial-Mesenchymal Transition / genetics
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Epithelial-Mesenchymal Transition / physiology*
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Extracellular Matrix / metabolism
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Female
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Humans
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Metalloproteases / metabolism
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Mice
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Molecular Targeted Therapy*
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Neoplasm Invasiveness
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Neoplasm Metastasis / prevention & control
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Nuclear Proteins / metabolism*
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Peptide Hydrolases / metabolism
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Receptors, Platelet-Derived Growth Factor / biosynthesis
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Receptors, Platelet-Derived Growth Factor / metabolism*
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Signal Transduction / drug effects
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Twist-Related Protein 1 / metabolism*
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src-Family Kinases / antagonists & inhibitors
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src-Family Kinases / metabolism
Substances
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Actins
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Nuclear Proteins
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TWIST1 protein, human
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Twist-Related Protein 1
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Receptors, Platelet-Derived Growth Factor
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src-Family Kinases
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Metalloproteases
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Peptide Hydrolases