Down-regulation of Gab1 inhibits cell proliferation and migration in hilar cholangiocarcinoma.
Down-regulation of Gab1 inhibits cell proliferation and migration in hilar cholangiocarcinoma.
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Gab1 的下调抑制肝门部胆管癌的细胞增殖和迁移。
DOI：
10.1371/journal.pone.0081347
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Liu J
中科院分区：
文献类型：
--
作者：
Sang H;Li T;Li H;Liu J
肝门部胆管癌是一种起源于肝门部胆管上皮的高度侵袭性恶性肿瘤。由于缺乏有效的综合治疗手段，肝门部胆管癌的预后较差。本研究首次采用免疫组化方法检测肝门部胆管癌实体瘤中Gab 1、VEGFR-2、MMP-9的表达，并分析其与临床病理特征的关系。利用siRNA干扰胆管癌细胞株ICBD-1，检测其PI 3 K/Akt信号通路、MMP-9水平及肿瘤细胞恶性生物学行为。数据显示，1. Gab 1、VEGFR-2、MMP-9在肝门部胆管癌组织中均呈高表达，且三者之间呈正相关，与淋巴结转移和分化程度有关。2.经Gab 1或VEGFR-2 siRNA干扰后，ICBD-1细胞PI 3 K/Akt通路活性和MMP-9水平均降低。同时细胞增殖能力下降，细胞周期阻滞于G1期，凋亡增加，侵袭能力下降。提示Gab 1、VEGFR-2和MMP-9的表达与肝门部胆管癌的恶性生物学行为密切相关。Gab 1通过VEGFR-2/Gab 1/PI 3 K/Akt信号通路调节肝门部胆管癌细胞的生长、凋亡和侵袭，并通过MMP-9影响肿瘤细胞的侵袭。
Hilar cholangiocarcinoma is a highly aggressive malignancy originating from the hilar biliary duct epithelium. Due to few effective comprehensive treatments, the prognosis of hilar cholangiocarcinoma is poor. In this study, immunohistochemistry was first used to detect and analyze the expression of Gab1, VEGFR-2, and MMP-9 in hilar cholangiocarcinoma solid tumors and the relationships to the clinical pathological features. Furthermore, Gab1 and VEGFR-2 siRNA were used to interfere the hilar cholangiocarcinoma cell line ICBD-1 and then detect the PI3K/Akt signaling pathway, MMP-9 levels and malignant biological behaviors of tumor cells. The data showed that 1. Gab1, VEGFR-2, and MMP-9 were highly expressed and positively correlated with each other in hilar cholangiocarcinoma tissues, which were related to lymph node metastasis and differentiation. 2. After Gab1 or VEGFR-2 siRNA interference, PI3K/Akt pathway activity and MMP-9 levels were decreased in ICBD-1 cells. At the same time, cell proliferation decreased, cell cycle arrested in G1 phase, apoptosis increased and invasion decreased. These results suggest that the expression of Gab1, VEGFR-2, and MMP-9 are significantly related to the malignant biological behavior of hilar cholangiocarcinoma. Gab1 regulates growth, apoptosis and invasion through the VEGFR-2/Gab1/PI3K/Akt signaling pathway in hilar cholangiocarcinoma cells and influences the invasion of tumor cells via MMP-9.
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影响因子：
15.9
作者：
Dias, S;Hattori, K;Rafii, S
通讯作者：
Rafii, S
影响因子：
4.8
作者：
Caron, Christine;Spring, Kathleen;Royal, Isabelle
通讯作者：
Royal, Isabelle
DOI：
10.1084/jem.20111424
发表时间：
2012-03-12
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Hamerlik P;Lathia JD;Rasmussen R;Wu Q;Bartkova J;Lee M;Moudry P;Bartek J Jr;Fischer W;Lukas J;Rich JN;Bartek J
通讯作者：
Bartek J
影响因子：
4.8
作者：
Laramee, Melanie;Chabot, Catherine;Royal, Isabelle
通讯作者：
Royal, Isabelle
影响因子：
3.7
作者：
Murakami, Yoshiaki;Uemura, Kenichiro;Sueda, Taijiro
通讯作者：
Sueda, Taijiro