CHL1 Is Expressed and Functions as a Malignancy Promoter in Glioma Cells.
CHL1 Is Expressed and Functions as a Malignancy Promoter in Glioma Cells.
复制标题
CHL1 在神经胶质瘤细胞中表达并充当恶性促进剂
DOI：
10.3389/fnmol.2017.00324
复制
发表时间：
2017
影响因子：
4.8
通讯作者：
Zhao WJ
中科院分区：
文献类型：
--
作者：
Yang Z;Xie Q;Hu CL;Jiang Q;Shen HF;Schachner M;Zhao WJ
与L1CAM同源的细胞黏附分子(CHL1)是细胞黏附分子L1(L1CAM)基因家族的成员。尽管CHL1在多种肿瘤中的表达和功能已有报道，但CHL1在胶质瘤发生发展中的作用尚不清楚。在本研究中，我们研究了CHL1对U-87 MG人脑胶质母细胞瘤、人脑胶质瘤U251和SHG-44细胞的增殖指数以及通过siRNA激活Akt1和Erk信号通路的影响。我们发现，针对CHL1的siRNA显著下调了CHL1的mRNA和蛋白的表达，并伴随着细胞增殖和侵袭能力的降低。下调CHL1的表达也降低了细胞存活率，增加了caspase-3的活性。在裸鼠U-87 MG细胞皮下移植瘤中，靶向CHL1的siRNA治疗显著下调了体内CHL1的表达，同时伴随着激活的caspase-3水平的增加。我们的联合结果首次证实，与大多数其他类型的癌症中发现的CHL1不同，CHL1在体外和体内都能促进人胶质瘤细胞的增殖、转移和迁移。这些结果表明CHL1是胶质瘤/胶质母细胞瘤临床治疗的靶点。
The cell adhesion molecule with homology to L1CAM (close homolog of L1) (CHL1) is a member of the cell adhesion molecule L1 (L1CAM) gene family. Although CHL1 expression and function have been reported in several tumors, the roles of CHL1 in the development of glioma remain unclear. In the present study, we investigated the effects of CHL1 on proliferation indexes and activation of Akt1 and Erk signaling by siRNA in U-87 MG human glioblastoma and human U251 and SHG-44 glioma cells. We found that siRNA targeting CHL1 significantly down-regulated the expression of CHL1 mRNA and protein accompanied by reduced cell proliferation and transmigration invasion in all three cell lines. Down-regulating CHL1 expression also reduced cell survival, as measured by the Bax/Bcl-2 ratio, and increased activation of caspase-3. In subcutaneous U-87 MG cell xenograft tumors in nude mice, intratumoral administration of siRNA targeting CHL1 treatment significantly down-regulated CHL1 expression in vivo, accompanied by increased levels of activated caspase-3. Our combined results confirmed for the first time that in contrast to findings about CHL1 in most other cancer types, CHL1 functions in promoting cell proliferation, metastasis and migration in human glioma cells both in vitro and in vivo. These results indicate that CHL1 is a therapeutic target in the clinical management of glioma/glioblastoma.
登录
查看更多内容
影响因子：
78.5
作者：
Collado, Manuel;Serrano, Manuel
通讯作者：
Serrano, Manuel
DOI：
10.1073/pnas.92.20.9363
发表时间：
1995-09-26
影响因子：
11.1
作者：
DIMRI, GP;LEE, XH;CAMPISI, J
通讯作者：
CAMPISI, J
影响因子：
4.8
作者：
Hitt, Brian;Riordan, Sean M.;Vassar, Robert
通讯作者：
Vassar, Robert
影响因子：
4
作者：
Higuchi, T;Fujiwara, H;Fujii, S
通讯作者：
Fujii, S
影响因子：
3.5
作者：
Huang, Xin;Zhu, Ling-ling;Fan, Ming
通讯作者：
Fan, Ming