Pigment epithelium-derived factor promotes tumor metastasis through an interaction with laminin receptor in hepatocellular carcinomas.
Pigment epithelium-derived factor promotes tumor metastasis through an interaction with laminin receptor in hepatocellular carcinomas.
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色素上皮衍生因子通过与肝细胞癌层粘连蛋白受体相互作用促进肿瘤转移
DOI：
10.1038/cddis.2017.359
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发表时间：
2017-08-03
影响因子：
9
通讯作者：
Li H
中科院分区：
文献类型：
--
作者：
Hou J;Ge C;Cui M;Liu T;Liu X;Tian H;Zhao F;Chen T;Cui Y;Yao M;Li J;Li H
色素上皮衍生因子（PEDF）在肿瘤转移中具有复杂的功能，但人们对PEDF及其受体在肝细胞癌（HCC）中的作用知之甚少。在这里，我们发现 PEDF 的高表达与 HCC 患者总生存期较短相关。 PEDF 的强制表达增强了 HCC 细胞在体外和体内的侵袭行为，而沉默 PEDF 表达则减少了迁移和侵袭。此外，PEDF表达通过ERK1/2信号通路导致细胞形态和上皮间质转化（EMT）相关标志物表达的变化，包括HCC细胞中N-cadherin和slug的上调以及E-cadherin的下调。我们的结果进一步表明，PEDF 可以与层粘连蛋白受体 (LR) 相互作用，LR 敲低减弱了 PEDF 诱导的迁移、侵袭和 EMT 相关标记物的变化。更重要的是，在临床HCC标本中，我们发现PEDF表达与LR的亚细胞定位相关，PEDF高表达和LR阳性表达预示着不良预后。总之，我们的结果证明了 PEDF/LR 轴在 HCC 中通过 ERK1/2 介导的 EMT 驱动转移中的新功能作用，并为 HCC 提供了一个有希望的预后标志物。
Pigment epithelium-derived factor (PEDF) has complex functions in tumor metastasis, but little is known about the roles of PEDF and its receptors in hepatocellular carcinoma (HCC). Here we found that high expression of PEDF is associated with shorter overall survival in HCC patients. Forced expression of PEDF enhanced HCC cell aggressive behavior in vitro and in vivo, whereas silencing PEDF expression reduced migration and invasion. Furthermore, PEDF expression led to changes in cell morphology and the expression of epithelial–mesenchymal transition (EMT)-related markers via ERK1/2 signaling pathway, including the upregulation of N-cadherin and slug, and the downregulation of E-cadherin in HCC cells. Our results further showed that PEDF could interact with laminin receptor (LR) and LR knockdown attenuated PEDF-induced migration, invasion and the change of EMT-related markers. More importantly, in clinical HCC specimens, we found that PEDF expression was correlated with subcellular localization of LR, and that high expression of PEDF and positive expression of LR predicted a poor prognosis. In conclusion, our results demonstrate a novel functional role of PEDF/LR axis in driving metastasis through ERK1/2-mediated EMT in HCC and provided a promising prognostic marker in HCC.
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影响因子：
4.8
作者：
Notari, Luigi;Baladron, Victoriano;Becerra, S. Patricia
通讯作者：
Becerra, S. Patricia
影响因子：
11.2
作者：
Chen H;Zhu G;Li Y;Padia RN;Dong Z;Pan ZK;Liu K;Huang S
通讯作者：
Huang S
影响因子：
2.7
作者：
Brabletz, T;Hlubek, F;Kirchner, T
通讯作者：
Kirchner, T
DOI：
10.1016/j.bbrc.2013.12.060
发表时间：
2014-01-17
影响因子：
3.1
作者：
Matsui, Takanori;Higashimoto, Yuichiro;Yamagishi, Sho-ichi
通讯作者：
Yamagishi, Sho-ichi
影响因子：
5.6
作者：
Omar, Aadilah;Reusch, Uwe;Weiss, Stefan F. T.
通讯作者：
Weiss, Stefan F. T.