Divergent behaviors and underlying mechanisms of cell migration and invasion in non-metastatic T24 and its metastatic derivative T24T bladder cancer cell lines.
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.
Zhejiang Provincial Key Laboratory for Technology & Application of Model Organisms, School of Life Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, China. Nelson Institute of Environmental Medicine, New York University School of Medicine, Tuxedo, NY, USA.
Honglei
H
Jin
Nelson Institute of Environmental Medicine, New York University School of Medicine, Tuxedo, NY, USA.
Yonghui
Y
Yu
Nelson Institute of Environmental Medicine, New York University School of Medicine, Tuxedo, NY, USA.
Young
Y
Hu
Nelson Institute of Environmental Medicine, New York University School of Medicine, Tuxedo, NY, USA.
Chris
C
Lu
Nelson Institute of Environmental Medicine, New York University School of Medicine, Tuxedo, NY, USA.
Jingxia
J
Li
Zhejiang Provincial Key Laboratory for Technology & Application of Model Organisms, School of Life Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, China.
Jiayan
J
Gu
Zhejiang Provincial Key Laboratory for Technology & Application of Model Organisms, School of Life Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, China.
Liping
L
Zhang
Zhejiang Provincial Key Laboratory for Technology & Application of Model Organisms, School of Life Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, China. Nelson Institute of Environmental Medicine, New York University School of Medicine, Tuxedo, NY, USA.
Haishan
H
Huang
Nelson Institute of Environmental Medicine, New York University School of Medicine, Tuxedo, NY, USA.
Dongyun
D
Zhang
Departments of Urology and Pathology, New York University School of Medicine, New York, NY, USA. Veterans Affairs New York Harbor Healthcare System Manhattan Campus, New York, NY, USA.
Xue-Ru
XR
Wu
Zhejiang Provincial Key Laboratory for Technology & Application of Model Organisms, School of Life Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, China.
Jimin
J
Gao
Zhejiang Provincial Key Laboratory for Technology & Application of Model Organisms, School of Life Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, China. Nelson Institute of Environmental Medicine, New York University School of Medicine, Tuxedo, NY, USA.
Chuanshu
C
Huang
D015153:Blotting, Western; D002295:Carcinoma, Transitional Cell / Q000473:pathology*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000502:physiology*; D006801:Humans; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013482:Superoxide Dismutase / Q000378:metabolism; D014162:Transfection; D001749:Urinary Bladder Neoplasms / Q000473:pathology*; D000099156:Superoxide Dismutase 2
D020778:Matrix Metalloproteinase 2; D013482:Superoxide Dismutase; D000099156:Superoxide Dismutase 2; C522361:MMP2 protein, human