Regulation of lamellipodia formation and cell invasion by CLIP-170 in invasive human breast cancer cells

被引：31

作者：

Suzuki, Katsuo ^{[1
]}

Takahashi, Kazuhide ^{[1
]}

机构：

[1] Kanagawa Canc Ctr, Res Inst, Mol Cell Biol Div, Asahi Ku, Yokohama, Kanagawa 2410815, Japan

来源：

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS | 2008年 / 368卷 / 02期

关键词：

Lamellipodia; cell invasion; Rac; IQGAP1; CLIP-170; Kinesin;

D O I：

10.1016/j.bbrc.2008.01.069

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Lamellipodia formation necessary for cell invasion is regulated by Rac1. We report here that lamellipodia formation and three-dimensional invasion were significantly promoted by HGF and serum, respectively, in invasive human breast cancer cells. Rac1 formed a complex with CLIP-170, IQGAP1, and kinesin in serum-starved cells, and stimulation of the cells with HGF and serum caused the partial release of IQGAP1 and kinesin from Rac1-CLIP-170 complex. The HGF-induced release of the proteins and promotion of lamellipodia formation were inhibited by an inhibitor of PI3K. Moreover, downregulation of CLIP-170 by siRNA released IQGAP1 and kinesin from Rac1 and promoted lamellipodia formation and invasion, independent of HGF and serum. The results suggest that promotion of lamellipodia formation and invasion by HGF or serum requires PI3K-dependent release of IQGAP1 and kinesin from Rac1-CLIP-170 complex and that CLIP-170 prevents cells from the extracellular stimulus-independent lamellipodia formation and invasion by tethering IQGAP1 and kinesin to Rac1. (C) 2008 Elsevier Inc. All rights reserved.

引用

页码：199 / 204

页数：6

共 30 条

[1] IQGAP1, a Rac- and Cdc42-binding protein, directly binds and cross-links microfilaments [J].

Bashour, AM ;

Fullerton, AT ;

Hart, MJ ;

Bloom, GS .

JOURNAL OF CELL BIOLOGY, 1997, 137 (07) :1555-1566

[2] Direct observation of dendritic actin filament networks nucleated by Arp2/3 complex and WASP/Scar proteins [J].

Blanchoin, L ;

Amann, KJ ;

Higgs, HN ;

Marchand, JB ;

Kaiser, DA ;

Pollard, TD .

NATURE, 2000, 404 (6781) :1007-1011

[3] IDENTIFICATION OF THE HEPATOCYTE GROWTH-FACTOR RECEPTOR AS THE C-MET PROTOONCOGENE PRODUCT [J].

BOTTARO, DP ;

RUBIN, JS ;

FALETTO, DL ;

CHAN, AML ;

KMIECIK, TE ;

VANDEWOUDE, GF ;

AARONSON, SA .

SCIENCE, 1991, 251 (4995) :802-804

[4] Regulation of the Rac1-specific exchange factor Tiam1 involves both phosphoinositide 3-kinase-dependent and -independent components [J].

Fleming, IN ;

Gray, A ;

Downes, CP .

BIOCHEMICAL JOURNAL, 2000, 351 :173-182

[5] Rac1 and Cdc42 capture microtubules through IQGAP1 and CLIP-170 [J].

Fukata, M ;

Watanabe, T ;

Noritake, J ;

Nakagawa, M ;

Yamaga, M ;

Kuroda, S ;

Matsuura, Y ;

Iwamatsu, A ;

Perez, F ;

Kaibuchi, K .

CELL, 2002, 109 (07) :873-885

[6] Regulation of cross-linking of actin filament by IQGAP1, a target for Cdc42 [J].

Fukata, M ;

Kuroda, S ;

Fujii, K ;

Nakamura, T ;

Shoji, I ;

Matsuura, Y ;

Okawa, K ;

Iwamatsu, A ;

Kikuchi, A ;

Kaibuchi, K .

JOURNAL OF BIOLOGICAL CHEMISTRY, 1997, 272 (47) :29579-29583

[7] THE CELLULAR FUNCTIONS OF SMALL GTP-BINDING PROTEINS [J].

HALL, A .

SCIENCE, 1990, 249 (4969) :635-640

[8] SUBMOLECULAR DOMAINS OF BOVINE BRAIN KINESIN IDENTIFIED BY ELECTRON-MICROSCOPY AND MONOCLONAL-ANTIBODY DECORATION [J].

HIROKAWA, N ;

PFISTER, KK ;

YORIFUJI, H ;

WAGNER, MC ;

BRADY, ST ;

BLOOM, GS .

CELL, 1989, 56 (05) :867-878

[9] Phosphoinositide 3-kinase activates Rac by entering in a complex with Eps8, Abi1, and Sos-1 [J].

Innocenti, M ;

Frittoli, E ;

Ponzanelli, I ;

Falck, JR ;

Brachmann, SM ;

Di Fiore, PP ;

Scita, G .

JOURNAL OF CELL BIOLOGY, 2003, 160 (01) :17-23

[10] Rac-WAVE2 signaling is involved in the invasive and metastatic phenotypes of murine melanoma cells [J].

Kurisu, S ;

Suetsugu, S ;

Yamazaki, D ;

Yamaguchi, H ;

Takenawa, T .

ONCOGENE, 2005, 24 (08) :1309-1319

← 1 2 3 →