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p63RhoGEF‐mediated formation of a single polarized lamellipodium is required for chemotactic migration in breast carcinoma cells
Author(s) -
Hayashi Aya,
Hiatari Ryuichi,
Tsuji Takuji,
Ohashi Kazumasa,
Mizuno Kensaku
Publication year - 2013
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2013.01.043
Subject(s) - chemotaxis , rhoa , lamellipodium , microbiology and biotechnology , pseudopodia , breast carcinoma , cell migration , chemistry , carcinoma cell , cancer research , biology , cell , signal transduction , cancer , medicine , breast cancer , tumor cells , actin , biochemistry , receptor
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.