Hepatoma-derived growth factor stimulates podosome rosettes formation in NIH/3T3 cells through the activation of phosphatidylinositol 3-kinase/Akt pathway

被引:24
作者
Kung, Mei-Lang [1 ]
Tsai, Han-En [2 ]
Hu, Tsung-Hui [4 ]
Kuo, Hsiao-Mei [5 ]
Liu, Li-Fen [6 ]
Chen, San-Cher [2 ,3 ]
Lin, Pey-Ru [7 ]
Ma, Yi-Ling [1 ]
Wang, E-Ming [1 ]
Liu, Guei-Sheung [8 ]
Liu, Jong-Kang [1 ]
Tai, Ming-Hong [1 ,2 ,3 ]
机构
[1] Natl Sun Yat Sen Univ, Dept Biol Sci, Kaohsiung 804, Taiwan
[2] Natl Sun Yat Sen Univ, Inst Biomed Sci, Kaohsiung 804, Taiwan
[3] Natl Sun Yat Sen Univ, Ctr Neurosci, Kaohsiung 804, Taiwan
[4] Chang Gung Univ, Coll Med, Chang Gung Mem Hosp,Dept Internal Med, Kaohsiung Med Ctr,Div Hepatogastroenter, Kaohsiung, Taiwan
[5] Chang Gung Univ, Coll Med, Chang Gung Mem Hosp, Dept Mitochondrial Res Unit,Kaohsiung Med Ctr, Kaohsiung, Taiwan
[6] I Shou Univ, Dept Biol Sci & Technol, Kaohsiung, Taiwan
[7] Natl Cheng Kung Univ, Inst Basic Med, Tainan 70101, Taiwan
[8] Univ Melbourne, OBrien Inst, Melbourne, Vic, Australia
关键词
Cell migration; Hepatoma-derived growth factor; Podosome; PI3K; Akt; GENE-TRANSFER; ENDOTHELIAL-CELLS; MIGRATION; CANCER; PROLIFERATION; INVADOPODIA; INHIBITION;
D O I
10.1016/j.bbrc.2012.07.060
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
Hepatoma-derived growth factor (HDGF) stimulates the migration, invasion and metastasis in several types of cancer cells. However, the mechanism underlying HDGF-stimulated migration remains unclear. In this study, we investigated the influence of HDGF on cytoskeleton remodeling and phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathway in non-transformed NIH/3T3 cells. Exogenous HDGF promoted the migration and the formation of dorsal ruffles and podosome rosettes. Besides, HDGF supply increased the PI3K expression and Akt phosphorylation in dose- and time-dependent manners. Application of LY294002, a PI3K inhibitor, attenuated the HDGF-induced migration, dorsal ruffles and podosome rosettes formation. Consistently, the HDGF-overexpressing NIH/3T3 transfectants exhibited significantly increased motility and elevated PI3K/Akt activities, which were repressed by LY294002 or adenovirus-mediated overexpression of endogenous PI3K antagonist, PTEN. In summary, HDGF elicits the activation of PI3K/Akt signaling cascade, thereby promoting cytoskeleton remodeling to stimulate cellular migration. (c) 2012 Elsevier Inc. All rights reserved.
引用
收藏
页码:169 / 176
页数:8
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