Cathepsin L is involved in X-ray-induced invasion and migration of human glioma U251 cells
Cathepsin L is involved in X-ray-induced invasion and migration of human glioma U251 cells
复制标题
组织蛋白酶 L 参与 X 射线诱导的人胶质瘤 U251 细胞的侵袭和迁移
DOI：
10.1016/j.cellsig.2016.10.012
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发表时间：
2017
影响因子：
4.8
通讯作者：
Liang Zhongqin
中科院分区：
文献类型：
--
作者：
Xiong Yajie;Ji Wenjun;Fei Yao;Zhao Yifan;Wang Long;Wang Wenjuan;Han Meilin;Tan Caihong;Fei Xifeng;Huang Qiang;Liang Zhongqin
胶质母细胞瘤是最常见的原发性脑肿瘤，放疗是治疗胶质母细胞瘤的重要方法。然而，最近一些研究报道，辐射也可以促进恶性肿瘤的侵袭和迁移。本文中，我们发现，与对照组相比，x线照射下的人胶质瘤U251细胞的迁移和侵袭性显著增加，并伴有组织蛋白酶L （CTSL）的增加，组织蛋白酶L是肿瘤细胞过度表达和分泌的一种溶酶体半胱氨酸蛋白酶。为了验证CTSL与x射线诱导的胶质瘤侵袭之间是否存在关系，我们使用CTSL特异性抑制剂z - fy - cho或短发夹RNA干扰预处理U251细胞。结果表明，下调CTSL可抑制细胞的侵袭和迁移。此外，与对照组相比，还检测到细胞信号分子Rho激酶的显著减少。我们还发现CTSL参与EMT的进展：无论是在体外还是在临床标本中。综上所述，我们的研究结果表明，CTSL是介导x射线诱导的人胶质瘤U251细胞侵袭和迁移的重要蛋白，抑制CTSL的表达可能通过降低RhoA和CDC42以及EMT阳性标记物的活性来减少U251细胞的侵袭。
An important therapeutic method of glioblastoma, the most common primary brain tumor, is radiotherapy. However, several studies reported recently that radiation could also promote the invasion and migration of malignant tumor. Herein, we have identified that a significant increase of migration and invasiveness of human glioma U251 cells undergoing X-ray was observed compared to controls, accompanied by the increase of cathepsin L (CTSL), which is a lysosomal cysteine protease overexpressed and secreted by tumor cells. To verify if there was a relationship between CTSL and the X-ray-induced glioma invasion, a CTSL specific inhibitorZ-FY-CHO or a short hairpin RNA interference was used to pretreat U251 cells. As a result, the cell invasion and migration was impaired via down-regulation of CTSL. Additionally, a marked reduction of the cell-signaling molecules Rho kinase was also detected compared with controls. We also found that CTSL is involved in EMT progress: both in vitro and in clinical specimens. Overall, our findings show that CTSL is an important protein which mediates cell invasion and migration of human glioma U251 cells induced by X-ray, and the inhibition of CTSL expression might diminish the invasion of U251 cells by reducing the activity of RhoA and CDC42 as well as EMT positive markers.