Divergent behaviors and underlying mechanisms of cell migration and invasion in non-metastatic T24 and its metastatic derivative T24T bladder cancer cell lines.
Divergent behaviors and underlying mechanisms of cell migration and invasion in non-metastatic T24 and its metastatic derivative T24T bladder cancer cell lines.
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DOI：
10.18632/oncotarget.2680
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发表时间：
2015-01-01
期刊：
影响因子：
--
通讯作者：
Huang C
中科院分区：
文献类型：
--
作者：
Jin H;Yu Y;Hu Y;Lu C;Li J;Gu J;Zhang L;Huang H;Zhang D;Wu XR;Gao J;Huang C
以前关于癌细胞侵袭的研究主要集中在它的迁移上，因为这两个事件通常被认为在生物学上是等价的。在此，我们发现T24T细胞表现出比T24细胞更高的侵袭力但更低的迁移能力。T24T细胞中Rho-GDPase的表达明显低于T24细胞，而SOD2的表达明显高于T24细胞。事实上，敲除T24T细胞中的SOD2可以逆转细胞的迁移，但不会影响细胞的侵袭。我们还发现SOD2抑制了JNK/c-jun级联反应，而通过异位表达TAM67抑制c-jun的激活则损害了T24T shSOD2细胞中Rho-GDPase的表达和细胞迁移。此外，我们还发现Sp1可以上调T24T细胞中SOD2的转录。重要的是，基质金属蛋白酶-2(MMP2)在T24T中高表达，并参与其侵袭力的增加，而MMP2的过表达是通过增加核仁的核转运而介导的，从而增强了MMP2mRNA的稳定性。综上所述，我们的研究揭示了人膀胱癌T24T细胞迁移和侵袭之间的负相关关系，并提示了SOD2和基质金属蛋白酶-2在调节人膀胱癌T24T细胞迁移和侵袭转移行为中的不同作用的新机制。
Previous studies on cancer cell invasion were primarily focused on its migration because these two events were often considered biologically equivalent. Here we found that T24T cells exhibited higher invasion but lower migration abilities than T24 cells. Expression of Rho-GDPases was much lower and expression of SOD2 was much higher in T24T cells than those in T24 cells. Indeed, knockdown of SOD2 in T24T cells can reverse the cell migration but without affecting cell invasion. We also found that SOD2 inhibited the JNK/c-Jun cascade, and the inhibition of c-Jun activation by ectopic expression of TAM67 impaired Rho-GDPases expression and cell migration in T24T shSOD2 cells. Further, we found that Sp1 can upregulate SOD2 transcription in T24T cells. Importantly, matrix metalloproteinase-2 (MMP-2) was overexpressed in T24T and participated in increasing its invasion, and MMP-2 overexpression was mediated by increasing nuclear transport of nucleolin, which enhanced mmp-2 mRNA stability. Taken together, our study unravels an inverse relationship between cell migration and invasion in human bladder cancer T24T cells and suggests a novel mechanism underlying the divergent roles of SOD2 and MMP-2 in regulating metastatic behaviors of human bladder T24T in cell migration and invasion.
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影响因子：
2.8
作者：
Hempel N;Carrico PM;Melendez JA
通讯作者：
Melendez JA
影响因子：
8
作者：
Huang, Q;Shen, HM;Ong, CN
通讯作者：
Ong, CN
影响因子：
--
作者：
Gao G;Chen L;Li J;Zhang D;Fang Y;Huang H;Chen X;Huang C
通讯作者：
Huang C
DOI：
10.1186/bcr2581
发表时间：
2010
期刊：
Breast cancer research : BCR
影响因子：
--
作者：
Foldynová-Trantírková S;Sekyrová P;Tmejová K;Brumovská E;Bernatík O;Blankenfeldt W;Krejcí P;Kozubík A;Dolezal T;Trantírek L;Bryja V
通讯作者：
Bryja V
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