title: p63RhoGEF-mediated formation of a single polarized lamellipodium is required for chemotactic migration in breast carcinoma cells.
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.
authors: Department of Biomolecular Sciences, Graduate School of Life Sciences, Tohoku University, Sendai, Miyagi 980-8578, Japan.
authors: Aya
authors: A
authors: Hayashi
authors: Ryuichi
authors: R
authors: Hiatari
authors: Takuji
authors: T
authors: Tsuji
authors: Kazumasa
authors: K
authors: Ohashi
authors: Kensaku
authors: K
authors: Mizuno
mesh_terms: D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D002277:Carcinoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D002633:Chemotaxis / Q000235:genetics*; D005260:Female; D015870:Gene Expression; D020662:Guanine Nucleotide Exchange Factors / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D057166:High-Throughput Screening Assays; D006801:Humans; D010957:Plasmids; D011554:Pseudopodia / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D034741:RNA, Small Interfering / Q000235:genetics*; D064067:Rho Guanine Nucleotide Exchange Factors; D044967:Serum / Q000737:chemistry; D014162:Transfection
chemical_list: C475063:ARHGEF25 protein, human; D020662:Guanine Nucleotide Exchange Factors; D034741:RNA, Small Interfering; D064067:Rho Guanine Nucleotide Exchange Factors