期刊
ONCOTARGET
卷 8, 期 21, 页码 34205-34222出版社
IMPACT JOURNALS LLC
DOI: 10.18632/oncotarget.11009
关键词
SNAIL; metastasis; circulating tumor cells; orthotopic xenografts; bladder cancer
资金
- NIH/NCI [SPORE P50 CA091846]
- Cancer Prevention Research Institute of Texas
- Dexter F. & Dorothy Baker Foundation
Epithelial-to-mesenchymal transition (EMT) has been implicated in the progression of bladder cancer. To study its contribution to bladder cancer metastasis, we established new xenograft models derived from human bladder cancer cell lines utilizing an orthotopic recycling technique that allowed us to isolate and examine the primary tumor and its corresponding circulating tumor cells (CTC's) and metastatic lesions. Using whole genome mRNA expression profiling, we found that a reversible epithelial-to-mesenchymal transition (EMT) characterized by TGF beta pathway activation and SNAIL expression was associated with the accumulation of CTCs. Finally, we observed that conditional silencing of SNAIL completely blocked CTC production and regional/distant metastasis. Using this unique bladder cancer xenograft model, we conclude that metastasis is dependent on a reversible EMT mediated by SNAIL.
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