Receptor for activated C kinase 1 (RACK1): a regulator for migration and invasion in oral squamous cell carcinoma cells

被引:29
作者
Li, Jing [1 ]
Guo, Yu [1 ]
Feng, Xiaodong [1 ]
Wang, Zhiyong [1 ]
Wang, Yun [1 ]
Deng, Peng [1 ]
Zhang, Dunfang [1 ]
Wang, Ruinan [1 ]
Xie, Liang [1 ]
Xu, Xiaoping [1 ]
Zhou, Yu [1 ]
Ji, Ning [1 ]
Hu, Jing [1 ]
Zhou, Min [1 ]
Liao, Ga [1 ]
Geng, Ning [1 ]
Jiang, Lu [1 ]
Wang, Zhi [1 ,2 ]
Chen, Qianming [1 ]
机构
[1] Sichuan Univ, State Key Lab Oral Dis, W China Coll Stomatol, Chengdu 610041, Sichuan, Peoples R China
[2] Sun Yat Sen Univ, Dept Oral Med, Guanghua Sch Stomatol, Guangzhou 510055, Guangdong, Peoples R China
基金
美国国家科学基金会; 中国国家自然科学基金;
关键词
RACK1; OSCC; Proliferation; Invasion; Adhesion; Migration; GROWTH-FACTOR-ALPHA; EXTRACELLULAR-MATRIX; PROTEIN; METASTASIS; ADHESION; CANCER; HEAD; NECK; CARCINOGENESIS; ANGIOGENESIS;
D O I
10.1007/s00432-011-1097-7
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Receptor of activated protein kinase C 1 (RACK1) has been identified as an anchoring or adaptor protein in multiple intracellular signal transduction pathways. Our previous study has showed that the expression of RACK1 was paralleled with proliferation and correlated with metastasis and clinical outcome. However, the underlined mechanism has not been uncovered. We first selected a most effective siRNA among three siRNAs (siRNA-1, siRNA-2 and siRNA-3) targeting different regions in the RACK1 mRNA and re-evaluated the anticancer effect of RACK1 silencing on HSC-3 and Cal-27 cell lines by cell growth inhibition. And then, we investigated whether knockdown of RACK1 could inhibit cell adhesion, migration and invasion in these two cell lines. To further understand the molecular mechanism of RACK1 in these processes, the expressions of EGFR, pEGFR, HER2, MMP-2 and MMP-9 were detected by western blot. We verified that the silence of RACK1 gene in two OSCC cell lines could not only inhibit cell proliferation but also decrease the invasion, migration and adhesion capability of the tumor cells. Further, western blot analysis deduced that it might be related to the decrease in protein expression of EGFR, pEGFR, HER2, MMP-2 and MMP-9. Our results clearly showed the significance of RACK1-induced OSCC cell migration, invasion and adhesion, which could explain the underlined mechanism of the effect of the gene on metastasis and clinical outcome. Also, our results confirmed its role to be a prognostic indicator and a promising drug target for OSCC cell metastasis.
引用
收藏
页码:563 / 571
页数:9
相关论文
共 31 条
[1]   Coordinate signaling by integrins and receptor tyrosine kinases in the regulation of G1 phase cell-cycle progression [J].
Assoian, RK ;
Schwartz, MA .
CURRENT OPINION IN GENETICS & DEVELOPMENT, 2001, 11 (01) :48-53
[2]   The PKC targeting protein RACK1 interacts with the Epstein-Barr virus activator protein BZLF1 [J].
Baumann, M ;
Gires, O ;
Kolch, W ;
Mischak, H ;
Zeidler, R ;
Pich, D ;
Hammerschmidt, W .
EUROPEAN JOURNAL OF BIOCHEMISTRY, 2000, 267 (12) :3891-3901
[3]   Matrix metalloproteinase-9 triggers the angiogenic switch during carcinogenesis [J].
Bergers, G ;
Brekken, R ;
McMahon, G ;
Vu, TH ;
Itoh, T ;
Tamaki, K ;
Tanzawa, K ;
Thorpe, P ;
Itohara, S ;
Werb, Z ;
Hanahan, D .
NATURE CELL BIOLOGY, 2000, 2 (10) :737-744
[4]   The anchoring protein RACK1 links protein kinase Cε to integrin β chains -: Requirement for adhesion and motility [J].
Besson, A ;
Wilson, TL ;
Yong, VW .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2002, 277 (24) :22073-22084
[5]   The interaction of Src and RACK1 is enhanced by activation of protein kinase C and tyrosine phosphorylation of RACK1 [J].
Chang, BY ;
Chiang, ML ;
Cartwright, CA .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2001, 276 (23) :20346-20356
[6]   Interactions between growth factor receptors and adhesion molecules: breaking the rules [J].
Comoglio, PM ;
Boccaccio, C ;
Trusolino, L .
CURRENT OPINION IN CELL BIOLOGY, 2003, 15 (05) :565-571
[7]  
Cortesina G, 2006, Acta Otorhinolaryngol Ital, V26, P317
[8]   The effect of the RACK1 signalling protein on the regulation of cell adhesion and cell contact guidance on nanometric grooves [J].
Dalby, Matthew J. ;
Hart, Andrew ;
Yarwood, Stephen John .
BIOMATERIALS, 2008, 29 (03) :282-289
[9]   Rack1 binds HIV-1 Nef and can act as a Nef-protein kinase C adaptor [J].
Gallina, A ;
Rossi, F ;
Milanesi, G .
VIROLOGY, 2001, 283 (01) :7-18
[10]  
GRANDIS JR, 1993, CANCER RES, V53, P3579