Overexpression of brachyury contributes to tumor metastasis by inducing epithelial-mesenchymal transition in hepatocellular carcinoma.
Overexpression of brachyury contributes to tumor metastasis by inducing epithelial-mesenchymal transition in hepatocellular carcinoma.
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DOI：
10.1186/s13046-014-0105-6
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发表时间：
2014-12-14
期刊：
影响因子：
--
通讯作者：
Kang J
中科院分区：
文献类型：
--
作者：
Du R;Wu S;Lv X;Fang H;Wu S;Kang J
Brachyury在多种人类恶性肿瘤中的过表达已有报道，但其在肝细胞癌进展和转移中的表达和功能尚不清楚。本研究旨在评价Brachyury在HCC转移中的关键作用。采用定量逆转录聚合酶链反应和免疫荧光方法分析了Brachyury在人肝癌（SMMC 7721、HepG 2、FHCC 98和Hep 3B）和对照细胞系中的表达。收集112例HCC患者的癌组织，采用免疫组化方法进行分析;对HCC组织进行芯片分析，以探讨HCC的临床病理学变量。Brachyury-SMMC 7721和Brachyury-HepG 2转染细胞的迁移和侵袭能力分别使用体外划痕伤口愈合和Matrigel侵袭测定来评估。此外，使用6周龄雄性BALB/c裸鼠（n = 10）模型进行体内测定。Brachyury在HCC中的表达高于癌旁组织（62.5%）。临床病理分析显示Brachyury表达与肝癌远处转移和预后不良密切相关。Brachyury的过表达促进了肝癌细胞的上皮间质转化（EMT）和体内外的转移。Brachyury过表达通过抑制磷酸酶和张力蛋白同源物（PTEN）增强Akt活化，这导致随后的Snail稳定，Snail是一种关键的EMT介质。研究结果表明，升高的Brachyury通过PTEN/Akt/Snail依赖性途径促进EMT促进HCC转移。Brachyury在HCC转移中起着关键作用，可能成为一种新的预后生物标志物和治疗靶点。
Brachyury overexpression has been reported in various human malignant neoplasms, but its expression and function in hepatocellular carcinoma progression and metastasis remains unknown. The present study aimed to evaluate the critical role of Brachyury in HCC metastasis. The expression of Brachyury in human HCC (SMMC7721, HepG2, FHCC98, and Hep3B) and control cell lines was analyzed using quantitative reverse-transcriptase polymerase chain reaction and immunoflourence methods. Cancerous tissues collected from patients with HCC (n = 112) were analyzed using immunohistochemical method; a microarray analysis of HCC tissues was performed to explore the clinicopathological variables of HCC. The migratory and invasive capacities of Brachyury-SMMC7721 and Brachyury-HepG2 transfected cells were evaluated using in vitro scratch wound healing and Matrigel invasion assays, respectively. Further, six-week-old male BALB/c nude mice (n = 10) model was used in vivo assay. Elevated expression of Brachyury was detected in HCCs (62.5%) compared with that in adjacent nontumorous tissues. Clinicopathological analysis revealed a close correlation of Brachyury expression with distant metastasis and poor prognosis of HCC. Overexpression of Brachyury promoted epithelial-mesenchymal transition (EMT) and metastasis of HCC cells in vitro and in vivo. Brachyury overexpression enhanced Akt activation by inhibiting phosphatase and tensin homolog (PTEN), which led to subsequent stabilization of Snail, a critical EMT mediator. The study findings suggest that elevated Brachyury facilitates HCC metastasis by promoting EMT via PTEN/Akt/Snail-dependent pathway. Brachyury plays a pivotal role in HCC metastasis and may serve as a novel prognostic biomarker and therapeutic target.
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影响因子：
5.2
作者：
Imajyo I;Sugiura T;Kobayashi Y;Shimoda M;Ishii K;Akimoto N;Yoshihama N;Kobayashi I;Mori Y
通讯作者：
Mori Y
DOI：
10.1158/1078-0432.ccr-11-3211
发表时间：
2012-07-15
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Roselli M;Fernando RI;Guadagni F;Spila A;Alessandroni J;Palmirotta R;Costarelli L;Litzinger M;Hamilton D;Huang B;Tucker J;Tsang KY;Schlom J;Palena C
通讯作者：
Palena C
影响因子：
3.1
作者：
Ning, Jinfeng;Liu, Wei;Xu, Shidong
通讯作者：
Xu, Shidong
影响因子：
4.6
作者：
Lim, Jormay;Thiery, Jean Paul
通讯作者：
Thiery, Jean Paul
影响因子：
21.3
作者：
Griffin, KJP;Kimelman, D
通讯作者：
Kimelman, D