Uehara Shota, Saito Koji, Asami Hisayo, Ohta Yasutaka
Division of Cell Biology, Department of Biosciences, School of Science, Kitasato University, Kanagawa, Japan.
Division of Cell Biology, Department of Biosciences, School of Science, Kitasato University, Kanagawa, Japan
Anticancer Res. 2017 Sep;37(9):4837-4844. doi: 10.21873/anticanres.11891.
BACKGROUND/AIM: The small GTPase ADP ribosylation factor 6 (ARF6) promotes carcinoma cell invasion and metastasis through remodeling of actin cytoskeleton and formation of pseudopod that is regulated by RAC. RHO GTPase activating protein 24 (ARHGAP24), a RAC-specific GTPase activating protein, binds to activated ARF6 and is recruited to the plasma membrane. The aim of the present study was to demonstrate if ARHGAP24 is involved in the ARF6-mediated formation of pseudopods in breast carcinoma cells.
The formation of pseudopods induced by activated ARF6 was monitored using MDA-MB-231 human breast carcinoma cells. The effect of knockdown of endogenous ARHGAP24 by siRNA was examined.
Knockdown of ARHGAP24 in MDA-MB-231 carcinoma cells increased the lifespan of pseudopods to retract, which resulted in increased length of pseudopods induced by activated ARF6. ARHGAP24 required a binding site of ARF6 to achieve ARF6-dependent actin remodeling.
ARHGAP24 may regulate pseudopod formation downstream of activated ARF6 in MDA-MB-231 human breast carcinoma cells.
背景/目的：小GTP酶ADP核糖基化因子6（ARF6）通过重塑肌动蛋白细胞骨架和形成由RAC调节的伪足来促进癌细胞的侵袭和转移。RHO GTP酶激活蛋白24（ARHGAP24）是一种RAC特异性GTP酶激活蛋白，它与活化的ARF6结合并被招募到质膜。本研究的目的是证明ARHGAP24是否参与ARF6介导的乳腺癌细胞伪足形成。
使用MDA-MB-231人乳腺癌细胞监测活化的ARF6诱导的伪足形成。检测了siRNA敲低内源性ARHGAP24的效果。
在MDA-MB-231癌细胞中敲低ARHGAP24可延长伪足缩回的寿命，这导致活化的ARF6诱导的伪足长度增加。ARHGAP24需要ARF6的结合位点来实现ARF6依赖性肌动蛋白重塑。
ARHGAP24可能在MDA-MB-231人乳腺癌细胞中活化的ARF6下游调节伪足形成。
