Activated signal transducer and activator of transcription (STAT) 3: Localization in focal adhesions and function in ovarian cancer cell motility

被引:222
作者
Silver, DL
Naora, H
Liu, JS
Cheng, WJ
Montell, DJ
机构
[1] Johns Hopkins Sch Med, Dept Biol Chem, Baltimore, MD 21205 USA
[2] Univ Texas, MD Anderson Canc Ctr, Dept Mol Therapeut, Houston, TX 77030 USA
[3] Univ Texas, MD Anderson Canc Ctr, Dept Pathol, Houston, TX 77030 USA
关键词
D O I
10.1158/0008-5472.CAN-03-3959
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Constitutive activation of the Janus-activated kinase/signal transducer and activator of transcription (STAT) pathway promotes the proliferation and survival of cancer cells in culture and is associated with various cancers, including those of the ovary. We found that constitutively activated STAT3 levels correlated with aggressive clinical behavior of ovarian carcinoma specimens. Furthermore, inhibition of STAT3 reduced the motility of ovarian cancer cells in vitro. Surprisingly, we found that activated STAT3 localized not only to nuclei but also to focal adhesions in these cells. Activated STAT3 coimmunoprecipitated with phosphorylated paxillin and focal adhesion kinase and required paxillin and Src for its localization to focal adhesions. These results suggest that Janus-activated kinase/STAT signaling may contribute to ovarian cancer cell invasiveness.
引用
收藏
页码:3550 / 3558
页数:9
相关论文
共 51 条
[41]   Stat3 activation by Src induces specific gene regulation and is required for cell transformation [J].
Turkson, J ;
Bowman, T ;
Garcia, R ;
Caldenhoven, E ;
De Groot, RP ;
Jove, R .
MOLECULAR AND CELLULAR BIOLOGY, 1998, 18 (05) :2545-2552
[42]   Paxillin and focal adhesion signalling [J].
Turner, CE .
NATURE CELL BIOLOGY, 2000, 2 (12) :E231-E236
[43]  
Volberg T, 2001, J CELL SCI, V114, P2279
[44]   Zyxin and paxillin proteins: focal adhesion plaque LIM domain proteins go nuclear [J].
Wang, Y ;
Gilmore, TD .
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH, 2003, 1593 (2-3) :115-120
[45]  
WATSON JM, 1990, CANCER RES, V50, P6959
[46]   Stat3 activation regulates the expression of vascular endothelial growth factor and human pancreatic cancer angiogenesis and metastasis [J].
Wei, DY ;
Le, XD ;
Zheng, LZ ;
Wang, LW ;
Frey, JA ;
Gao, AC ;
Peng, ZH ;
Huang, SY ;
Xiong, HQ ;
Abbruzzese, JL ;
Xie, KP .
ONCOGENE, 2003, 22 (03) :319-329
[47]   Activated Src protein tyrosine kinase is overexpressed in late-stage human ovarian cancers [J].
Wiener, JR ;
Windham, TC ;
Estrella, VC ;
Parikh, NU ;
Thall, PF ;
Deavers, MT ;
Bast, RC ;
Mills, GB ;
Gallick, GE .
GYNECOLOGIC ONCOLOGY, 2003, 88 (01) :73-79
[48]   Focal adhesion kinase activates Stat1 in integrin-mediated cell migration and adhesion [J].
Xie, B ;
Zhao, JH ;
Kitagawa, M ;
Durbin, J ;
Madri, JA ;
Guan, JL ;
Fu, XY .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2001, 276 (22) :19512-19523
[49]   Stat3 controls cell movements during zebrafish gastrulation [J].
Yamashita, S ;
Miyagi, C ;
Carmany-Rampey, A ;
Shimizu, T ;
Fujii, R ;
Schier, AF ;
Hirano, T .
DEVELOPMENTAL CELL, 2002, 2 (03) :363-375
[50]   Janus kinase 2 is involved in stromal cell-derived factor-1α-induced tyrosine phosphorylation of focal adhesion proteins and migration of hematopoietic progenitor cells [J].
Zhang, XF ;
Wang, JF ;
Matczak, E ;
Proper, J ;
Groopman, JE .
BLOOD, 2001, 97 (11) :3342-3348