CD44s signals the acquisition of the mesenchymal phenotype required for anchorage-independent cell survival in hepatocellular carcinoma.
CD44s signals the acquisition of the mesenchymal phenotype required for anchorage-independent cell survival in hepatocellular carcinoma.
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DOI：
10.1038/bjc.2013.759
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发表时间：
2014-02-18
影响因子：
8.8
通讯作者：
Baba, H.
中科院分区：
文献类型：
--
作者：
Okabe, H.;Ishimoto, T.;Mima, K.;Nakagawa, S.;Hayashi, H.;Kuroki, H.;Imai, K.;Nitta, H.;Saito, S.;Hashimoto, D.;Chikamoto, A.;Ishiko, T.;Watanabe, M.;Nagano, O.;Beppu, T.;Saya, H.;Baba, H.
循环肿瘤细胞（CTC）在转移过程中起着重要作用，但其基本特征的细节仍然难以捉摸。我们假设表达CD44的CTC表现出间充质表型，并且在肝细胞癌（HCC）中具有较高的存活潜力。循环中的CD44+CD90+细胞，以前被证明是肿瘤起始细胞，从人血液中分选出来，并将其遗传特征与原发组织中的肿瘤细胞进行比较。在体外研究了循环系统中表达CD44的细胞的高存活潜力的机制。血液中CD44+CD90+细胞获得上皮间质转化，CD44表达由组织向血液显著增加。在Li7和HLE细胞中，CD44high群体比CD44low群体显示出更高的抗失巢凋亡和球形成能力。发现这种差异归因于CD44high群体中Twist 1和Akt信号的上调。Twist 1敲除显示HLE细胞的失巢凋亡抗性、球体形成和Akt信号显着降低。此外，间充质标志物和CD44 s表达在Twist 1敲低中下调。CD44 s象征着获得调节锚定独立能力的间充质表型。外周血中表达CD44 s的肿瘤细胞是HCC临床上重要的治疗靶点。
Circulating tumour cells (CTCs) have an important role in metastatic processes, but details of their basic characteristics remain elusive. We hypothesised that CD44-expressing CTCs show a mesenchymal phenotype and high potential for survival in hepatocellular carcinoma (HCC). Circulating CD44+CD90+ cells, previously shown to be tumour-initiating cells, were sorted from human blood and their genetic characteristics were compared with those of tumour cells from primary tissues. The mechanism underlying the high survival potential of CD44-expressing cells in the circulatory system was investigated in vitro. CD44+CD90+ cells in the blood acquired epithelial–mesenchymal transition, and CD44 expression remarkably increased from the tissue to the blood. In Li7 and HLE cells, the CD44high population showed higher anoikis resistance and sphere-forming ability than did the CD44low population. This difference was found to be attributed to the upregulation of Twist1 and Akt signal in the CD44high population. Twist1 knockdown showed remarkable reduction in anoikis resistance, sphere formation, and Akt signal in HLE cells. In addition, mesenchymal markers and CD44s expression were downregulated in the Twist1 knockdown. CD44s symbolises the acquisition of a mesenchymal phenotype regulating anchorage-independent capacity. CD44s-expressing tumour cells in peripheral blood are clinically important therapeutic targets in HCC.
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影响因子：
64.8
作者：
GALLATIN, WM;WEISSMAN, IL;BUTCHER, EC
通讯作者：
BUTCHER, EC
影响因子：
50.3
作者：
Ishimoto, Takatsugu;Nagano, Osamu;Saya, Hideyuki
通讯作者：
Saya, Hideyuki
影响因子：
11.2
作者：
Chiba, Tetsuhiro;Miyagi, Satoru;Iwama, Atsushi
通讯作者：
Iwama, Atsushi
影响因子：
15.9
作者：
Brown, Rhonda L.;Reinke, Lauren M.;Cheng, Chonghui
通讯作者：
Cheng, Chonghui
影响因子：
23.9
作者：
Lee, Terence Kin Wah;Castilho, Antonia;Irene Oi Lin Ng
通讯作者：
Irene Oi Lin Ng