Overexpression of SMC4 activates TGFβ/Smad signaling and promotes aggressive phenotype in glioma cells.
Overexpression of SMC4 activates TGFβ/Smad signaling and promotes aggressive phenotype in glioma cells.
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SMC4 的过度表达激活 TGF beta/Smad 信号传导并促进神经胶质瘤细胞的侵袭性表型
DOI：
10.1038/oncsis.2017.8
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发表时间：
2017-03-13
期刊：
影响因子：
6.2
通讯作者：
Li J
中科院分区：
文献类型：
--
作者：
Jiang L;Zhou J;Zhong D;Zhou Y;Zhang W;Wu W;Zhao Z;Wang W;Xu W;He L;Ma Y;Hu Y;Zhang W;Li J
4号染色体结构维持蛋白（structural maintenance of chromosomes 4，SMC 4）的过表达与肿瘤细胞的生长、迁移和侵袭有关，并与肿瘤患者的预后不良有关。然而，其临床意义和在胶质瘤中的生物学作用尚不清楚。在此，我们发现SMC 4在mRNA和蛋白水平上的表达在胶质瘤细胞和临床组织中显著增加，并且与不良预后相关。SMC 4过表达可显著促进胶质瘤细胞的增殖、迁移和侵袭能力，而下调SMC 4则可降低其增殖、迁移和侵袭能力，而且SMC 4转染胶质瘤细胞后转化生长因子β（TGFβ）/Smad信号通路被激活，而SMC 4沉默胶质瘤细胞后则被抑制，这一信号通路参与了SMC 4介导的胶质瘤细胞侵袭性。我们的研究结果为SMC 4的肿瘤功能和TGFβ/Smad通路在胶质瘤中过度活化的机制提供了新的见解，表明SMC 4是胶质瘤中有价值的预后因子和潜在的治疗靶点。
Overexpression of structural maintenance of chromosomes 4 (SMC4) has been reported to be involved in tumor cell growth, migration and invasion, and to be correlated with poor prognosis of cancer patient. However, its clinical significance and biological role in glioma remain unknown. Herein, we found that SMC4 expression at both mRNA and protein level was markedly increased in glioma cells and clinical tissues and that it correlated with poor prognosis. SMC4 overexpression markedly promoted the glioma cell proliferation rate and migration and invasive capability in vitro and in vivo, whereas SMC4 downregulation reduced it. Moreover, the transforming growth factor β (TGFβ)/Smad signaling pathway, which was activated in SMC4-transduced glioma cells and inhibited in SMC4-silenced glioma cells, contributed to SMC4-mediated glioma cell aggressiveness. Our results provide new insight into the oncofunction of SMC4 and the mechanism by which the TGFβ/Smad pathway is hyperactivated in gliomas, indicating that SMC4 is a valuable prognostic factor and a potential therapeutic target in gliomas.
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影响因子：
4
作者：
Jinushi, Takafumi;Shibayama, Yoshihiko;Kinoshita, Ichiro;Oizumi, Satoshi;Jinushi, Masahisa;Aota, Tadahiro;Takahashi, Toshiyuki;Horita, Shoichi;Dosaka-Akita, Hirotoshi;Iseki, Ken
通讯作者：
Iseki, Ken
影响因子：
16.6
作者：
Avgustinova A;Iravani M;Robertson D;Fearns A;Gao Q;Klingbeil P;Hanby AM;Speirs V;Sahai E;Calvo F;Isacke CM
通讯作者：
Isacke CM
影响因子：
15.9
作者：
Ostrom, Quinn T.;Gittleman, Haley;Barnholtz-Sloan, Jill S.
通讯作者：
Barnholtz-Sloan, Jill S.
影响因子：
5.2
作者：
Neganova, Irina;Vilella, Felipe;Lako, Majlinda
通讯作者：
Lako, Majlinda
影响因子：
4.8
作者：
Gabayan, AJ;Green, SB;Stea, B
通讯作者：
Stea, B