Oncotarget

Research Papers:

Divergent behaviors and underlying mechanisms of cell migration and invasion in non-metastatic T24 and its metastatic derivative T24T bladder cancer cell lines

Honglei Jin, Yonghui Yu, Young Hu, Chris Lu, Jingxia Li, Jiayan Gu, Liping Zhang, Haishan Huang, Dongyun Zhang, Xue-Ru Wu, Jimin Gao and Chuanshu Huang _

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Oncotarget. 2015; 6:522-536. https://doi.org/10.18632/oncotarget.2680

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Abstract

Honglei Jin1,2,*, Yonghui Yu2,*, Young Hu2, Chris Lu2, Jingxia Li2, Jiayan Gu1, Liping Zhang1, Haishan Huang1,2, Dongyun Zhang2, Xue-Ru Wu3,4, Jimin Gao1 and Chuanshu Huang1,2

1 Zhejiang Provincial Key Laboratory for Technology & Application of Model Organisms, School of Life Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, China

2 Nelson Institute of Environmental Medicine, New York University School of Medicine, Tuxedo, NY, USA

3 Departments of Urology and Pathology, New York University School of Medicine, New York, NY, USA

4 Veterans Affairs New York Harbor Healthcare System Manhattan Campus, New York, NY, USA

* These authors contributed equally to this work

Correspondence:

Chuanshu Huang, email:

Jimin Gao, email:

Keywords: bladder cancer; migration; invasion; SOD2; MMP-2

Received: August 25, 2014 Accepted: November 04, 2014 Published: November 04, 2014

Abstract

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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