title: Sox4 Expression Confers Bladder Cancer Stem Cell Properties and Predicts for Poor Patient Outcome.
abstract: 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.
authors.affiliation: 1. Department of Cancer Genetics;
authors.forename: He
authors.initials: H
authors.lastname: Shen
authors.affiliation: 1. Department of Cancer Genetics; ; 4. VU medical center, Cancer Center Amsterdam, Laboratory Medical Oncology, De Boelelaan 1118, 1081 HV Amsterdam, The Netherlands;
authors.forename: Maxime
authors.initials: M
authors.lastname: Blijlevens
authors.affiliation: 1. Department of Cancer Genetics;
authors.forename: Nuo
authors.initials: N
authors.lastname: Yang
authors.affiliation: 1. Department of Cancer Genetics;
authors.forename: Costakis
authors.initials: C
authors.lastname: Frangou
authors.affiliation: 1. Department of Cancer Genetics;
authors.forename: Kayla E
authors.initials: KE
authors.lastname: Wilson
authors.affiliation: 2. Department of Pathology;
authors.forename: Bo
authors.initials: B
authors.lastname: Xu
authors.affiliation: 1. Department of Cancer Genetics; ; 5. Orthopaedic Oncology Institute, Tangdu Hospital, Fourth Military Medical University, Xi'an, Shaanxi 710032, P.R. China;
authors.forename: Yinglong
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: 1. Department of Cancer Genetics; ; 6. Department of Gynecology and Obstetrics, The First Affiliated Hospital of Xi'an Jiaotong University School of Medicine, Xi'an, Shaanxi 710061, P.R. China.
authors.forename: Lirui
authors.initials: L
authors.lastname: Zhang
authors.affiliation: 2. Department of Pathology;
authors.forename: Carl D
authors.initials: CD
authors.lastname: Morrison
authors.affiliation: 3. Center for Biostatistics & Bioinformatics, Roswell Park Cancer Institute, Elm & Carlton Streets, Buffalo NY 14263;
authors.forename: Lori
authors.initials: L
authors.lastname: Shepherd
authors.affiliation: 3. Center for Biostatistics & Bioinformatics, Roswell Park Cancer Institute, Elm & Carlton Streets, Buffalo NY 14263;
authors.forename: Qiang
authors.initials: Q
authors.lastname: Hu
authors.affiliation: 3. Center for Biostatistics & Bioinformatics, Roswell Park Cancer Institute, Elm & Carlton Streets, Buffalo NY 14263;
authors.forename: Qianqian
authors.initials: Q
authors.lastname: Zhu
authors.affiliation: 3. Center for Biostatistics & Bioinformatics, Roswell Park Cancer Institute, Elm & Carlton Streets, Buffalo NY 14263;
authors.forename: Jianmin
authors.initials: J
authors.lastname: Wang
authors.affiliation: 3. Center for Biostatistics & Bioinformatics, Roswell Park Cancer Institute, Elm & Carlton Streets, Buffalo NY 14263;
authors.forename: Song
authors.initials: S
authors.lastname: Liu
authors.affiliation: 1. Department of Cancer Genetics;
authors.forename: Jianmin
authors.initials: J
authors.lastname: Zhang
mesh_terms: D014408:Biomarkers, Tumor / Q000235:genetics; D002295:Carcinoma, Transitional Cell / Q000235:genetics* / Q000473:pathology; D045744:Cell Line, Tumor; D002896:Chromosomes, Human, Pair 6; D015331:Cohort Studies; D058750:Epithelial-Mesenchymal Transition; D006801:Humans; D014411:Neoplastic Stem Cells / Q000473:pathology*; D011379:Prognosis; D055751:SOXC Transcription Factors / Q000235:genetics*; D001749:Urinary Bladder Neoplasms / Q000235:genetics* / Q000473:pathology
chemical_list: D014408:Biomarkers, Tumor; C083431:SOX4 protein, human; D055751:SOXC Transcription Factors
keywords: Sox4; bladder cancer; bladder cancer stem cell; chromosome 6p22 amplification