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
  • [1] The tight junction protein ZO-1 and an interacting transcription factor regulate ErbB-2 expression
    Balda, MS
    Matter, K
    [J]. EMBO JOURNAL, 2000, 19 (09) : 2024 - 2033
  • [2] The JAK/STAT pathway is required for border cell migration during Drosophila oogenesis
    Beccari, S
    Teixeira, L
    Rorth, P
    [J]. MECHANISMS OF DEVELOPMENT, 2002, 111 (1-2) : 115 - 123
  • [3] Interleukin-10 in serous ovarian carcinoma cell lines
    Berger, S
    Siegert, A
    Denkert, C
    Köbel, M
    Hauptmann, S
    [J]. CANCER IMMUNOLOGY IMMUNOTHERAPY, 2001, 50 (06) : 328 - 333
  • [4] Integrin LFA-1 interacts with the transcriptional co-activator JAB1 to modulate AP-1 activity
    Bianchi, E
    Denti, S
    Granata, A
    Bossi, G
    Geginat, J
    Villa, A
    Rogge, L
    Pardi, R
    [J]. NATURE, 2000, 404 (6778) : 617 - +
  • [5] Armadillo/β-catenin signals in the nucleus -: proof beyond a reasonable doubt?
    Bienz, M
    Clevers, H
    [J]. NATURE CELL BIOLOGY, 2003, 5 (03) : 179 - 182
  • [6] Stat3 as an oncogene
    Bromberg, JF
    Wrzeszczynska, MH
    Devgan, G
    Zhao, YX
    Pestell, RG
    Albanese, C
    Darnell, JE
    [J]. CELL, 1999, 98 (03) : 295 - 303
  • [7] Buettner R, 2002, CLIN CANCER RES, V8, P945
  • [8] Inhibition of constitutively active Stat3 suppresses growth of human ovarian and breast cancer cells
    Burke, WM
    Jin, XH
    Lin, HJ
    Huang, M
    Liu, R
    Reynolds, RK
    Lin, JY
    [J]. ONCOGENE, 2001, 20 (55) : 7925 - 7934
  • [9] Src catalytic but not scaffolding function is needed for integrin-regulated tyrosine phosphorylation, cell migration, and cell spreading
    Cary, LA
    Klinghoffer, RA
    Sachsenmaier, C
    Cooper, JA
    [J]. MOLECULAR AND CELLULAR BIOLOGY, 2002, 22 (08) : 2427 - 2440
  • [10] Constitutive activation of Stat3 signaling confers resistance to apoptosis in human U266 myeloma cells
    Catlett-Falcone, R
    Landowski, TH
    Oshiro, MM
    Turkson, J
    Levitzki, A
    Savino, R
    Ciliberto, G
    Moscinski, L
    Fernández-Luna, JL
    Nuñez, G
    Dalton, WS
    Jove, R
    [J]. IMMUNITY, 1999, 10 (01) : 105 - 115