期刊
INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES
卷 11, 期 12, 页码 1363-1375出版社
IVYSPRING INT PUBL
DOI: 10.7150/ijbs.13240
关键词
bladder cancer; chromosome 6p22 amplification; Sox4; bladder cancer stem cell
资金
- National Natural Science Fund of China [81202055]
- Roswell Park Cancer Institute
- National Cancer Institute (NCI) [P30 CA016056, R21 CA179693]
- Roswell Park Alliance Foundation
- American Cancer Society Research Scholar Grant [RSG-14-214-01-TBE]
Genetic and epigenetic alterations have been identified as to contribute directly or indirectly to the generation of transitional cell carcinoma of the urinary bladder (TCC-UB). We have previously found that amplification of chromosome 6p22 is significantly associated with the muscle-invasive rather than superficial TCC-UB. Here, we demonstrated that Sox4, one of the candidate oncogenes located within the chromosome 6p22 amplicon, confers bladder cancer stem cell (CSC) properties. Down-regulation of Sox4 led to the inhibition of cell migration, colony formation as well as mesenchymal-to-epithelial transition (MET). Interestingly, knockdown of Sox4 also reduced the sphere formation, enriched cell population with high levels of aldehyde dehydrogenase (ALDH(high)) and tumor formation potential. Using gene expression profiling, we further identified novel Sox4 target genes. Last, immunohistochemistry analysis of human bladder tumor tissue microarrays (TMAs) indicated that high Sox4 expression was correlated with advanced cancer stages and poor survival rate. In summary, our data show that Sox4 is an important regulator of the bladder CSC properties and it may serve as a biomarker of the aggressive phenotype in bladder cancer.
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