A novel role for signal transducer and activator of transcription 5b (STAT5b) in beta1-integrin-mediated human breast cancer cell migration.
A novel role for signal transducer and activator of transcription 5b (STAT5b) in beta1-integrin-mediated human breast cancer cell migration.
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DOI：
10.1186/bcr2341
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发表时间：
2009
期刊：
影响因子：
--
通讯作者：
Silva CM
中科院分区：
文献类型：
--
作者：
Bernaciak TM;Zareno J;Parsons JT;Silva CM
信号转导和转录激活因子（STAT）5 b是一种转录因子，参与许多实体瘤（包括乳腺癌）的促增殖和促存活信号传导。STAT 5 b对乳腺癌细胞运动性的贡献尚未被探索。本研究旨在阐明STAT 5 b在乳腺癌细胞迁移中的作用。在两种侵袭性的、高度迁移的乳腺癌细胞系（BT-549和MDA-MB-231）中通过使用siRNA敲低STAT 5 b，并进行transwell迁移测定以确定STAT 5 b对其迁移的重要性。敲低-拯救实验用于验证STAT 5 b敲低的特异性并确定STAT 5 b的哪些区域/功能对于其在迁移中的作用是必需的。进行伤口愈合和蔓延的活细胞成像，以检查STAT 5 b敲除后的细胞形态和运动性。STAT 5 b的敲除（而非STAT 5a）可抑制BT-549和MDA-MB-231乳腺癌细胞向血清迁移60%至80%，并在一定血清浓度范围内（0.1%至10%血清）同等抑制迁移。通过重新引入野生型STAT 5 b以及Y 699 F-和显性负性STAT 5 b突变体，但不是SH 2结构域缺陷型R618 K-STAT 5 b突变体，可以挽救STAT 5 b敲低后的迁移抑制。β1-整合素介导的乳腺癌细胞向纤连蛋白的迁移被STAT 5 b敲低抑制，并且STAT 5 b的丢失与定向迁移的丢失和附着于纤连蛋白后多个高度收缩性突起的形成相关。本文提供的数据表明，STAT 5 b是乳腺癌细胞迁移的组成部分，并确定了STAT 5 b在调节β1-整联蛋白介导的高度侵袭性乳腺癌细胞迁移中的一种新的SH 2依赖性功能。
Signal transducer and activator of transcription (STAT) 5b is a transcription factor involved in pro-proliferative and pro-survival signaling in a number of solid tumors, including breast cancer. The contribution of STAT5b to breast cancer cell motility has not been explored. This work aims to elucidate the role of STAT5b in breast cancer cell migration. STAT5b was knocked down by using siRNA in two aggressive, highly migratory breast cancer cell lines (BT-549 and MDA-MB-231), and transwell migration assays were performed to determine the importance of STAT5b for their migration. Knockdown-rescue experiments were used to validate the specificity of STAT5b knockdown and to determine which regions/functions of STAT5b are necessary for its role in migration. Live-cell imaging of wound healing and spreading was carried out to examine cell morphology and motility after STAT5b knockdown. Knockdown of STAT5b, but not STAT5a, inhibited migration of BT-549 and MDA-MB-231 breast cancer cells to serum by 60% to 80%, and inhibited migration equally over a range of serum concentrations (0.1% to 10% serum). Migratory inhibition upon STAT5b knockdown could be rescued by reintroduction of wild-type STAT5b, as well as Y699F- and dominant-negative STAT5b mutants, but not an SH2 domain defective R618K-STAT5b mutant. β1- integrin-mediated migration of breast cancer cells to fibronectin was inhibited with STAT5b knockdown, and loss of STAT5b correlated with loss of directional migration and formation of multiple, highly contractile protrusions upon attachment to fibronectin. The data presented here demonstrate that STAT5b is integral to breast cancer cell migration and identify a novel, SH2-dependent function of STAT5b in regulating β1-integrin-mediated migration of highly aggressive breast cancer cells.
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DOI：
10.1006/mcbr.2000.0231
发表时间：
2000-05-01
期刊：
Molecular Cell Biology Research Communications
影响因子：
--
作者：
de Groot, Rolf P.;Raaijmakers, Jan A. M.;Koenderman, Leo
通讯作者：
Koenderman, Leo
DOI：
10.1073/pnas.94.14.7239
发表时间：
1997-07-08
影响因子：
11.1
作者：
Udy, GB;Towers, RP;Davey, HW
通讯作者：
Davey, HW
影响因子：
8
作者：
Yamashita, H;Iwase, H;Fujii, Y
通讯作者：
Fujii, Y
影响因子：
4.8
作者：
Kloth, MT;Laughlin, KK;Silva, CM
通讯作者：
Silva, CM
影响因子：
11.4
作者：
Matsumura, I;Kitamura, T;Kanakura, Y
通讯作者：
Kanakura, Y