Abstract
Short hairpin RNAs targeting 66 Rho-GEFs were screened for inhibition of chemotaxis. Six Rho-GEFs (p63RhoGEF, Trio, Duet, Net1, Frabin/Fgd4, and AAH33666) were found to be required for the serum-induced chemotactic migration of MDA-MB-231 human breast carcinoma cells. Knockdown of p63RhoGEF suppressed serum-induced RhoA activation and chemotaxis and caused the aberrant formation of multiple lamellipodial protrusions after serum stimulation while control cells formed a single polarized lamellipodium. These results indicate that p63RhoGEF plays a crucial role in serum-induced chemotaxis by limiting lamellipodial protrusion to one direction via RhoA activation.
Copyright © 2013 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Breast Neoplasms / genetics*
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Breast Neoplasms / metabolism
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Breast Neoplasms / pathology
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Carcinoma / genetics*
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Carcinoma / metabolism
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Carcinoma / pathology
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Cell Line, Tumor
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Chemotaxis / genetics*
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Female
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Gene Expression
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Guanine Nucleotide Exchange Factors / antagonists & inhibitors
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Guanine Nucleotide Exchange Factors / genetics*
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Guanine Nucleotide Exchange Factors / metabolism
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High-Throughput Screening Assays
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Humans
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Plasmids
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Pseudopodia / genetics*
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Pseudopodia / metabolism
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Pseudopodia / pathology
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RNA, Small Interfering / genetics*
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Rho Guanine Nucleotide Exchange Factors
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Serum / chemistry
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Transfection
Substances
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ARHGEF25 protein, human
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Guanine Nucleotide Exchange Factors
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RNA, Small Interfering
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Rho Guanine Nucleotide Exchange Factors