title: SATB1 overexpression regulates the development and progression in bladder cancer through EMT.
abstract: The global gene regulator Special AT-rich sequence-binding protein-1 (SATB1) has been reported to induce EMT-like changes and be associated with poor clinical outcome in several cancers. This study aims to evaluate whether SATB1 affects the biological behaviors of bladder transitional cell carcinoma (BTCC) and further elucidate if this effect works through an epithelial-mesenchymal transition (EMT) pathway. The expression of SATB1, E-cadherin (epithelial markers), vimentin (mesenchymal markers) in BTCC tissues and adjacent noncancerous tissues, as well as in two cell lines of bladder cancer were investigated. Whether the SATB1 expression is associated with clinicopathological factors or not was statistically analyzed. Cell invasion and migration, cell cycle, cell proliferation and apoptosis were evaluated in SATB1 knockdown and overexpressed cell lines. Our results showed that the expression of SATB1 was remarkably up-regulated both in BTCC tissues and in bladder cancer cell lines with high potential of metastasis. The results were also associated with EMT markers and poor prognosis of BTCC patients. Moreover, SATB1 induced EMT processes through downregulation of E-cadherin, upregulation of E-cadherin repressors (Snail, Slug and vimentin). SATB1 also promoted cell cycle progression, cell proliferation, cell invasion and cell migration, but did not alter cell survival. In conclusion, our results suggest that SATB1 plays a crucial role in the progression of bladder cancer by regulating genes controlling EMT processes. Further, it may be a novel therapeutic target for aggressive bladder cancers.
authors.affiliation: Department of Urology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, Hubei, PR China.
authors.forename: Feng
authors.initials: F
authors.lastname: Wan
authors.affiliation: Department of General Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, Hubei, PR China.
authors.forename: Chao
authors.initials: C
authors.lastname: Cheng
authors.affiliation: Department of Urology Massachusetts General Hospital, Harvard Medical School, 55 Fruit St, Warren Building 317, Boston, MA, 02114, United States of America.
authors.forename: Zongwei
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Department of Urology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, Hubei, PR China.
authors.forename: Xingyuan
authors.initials: X
authors.lastname: Xiao
authors.affiliation: Department of Urology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, Hubei, PR China.
authors.forename: Hanqing
authors.initials: H
authors.lastname: Zeng
authors.affiliation: Central Laboratory of Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, Hubei, PR China.
authors.forename: Shian
authors.initials: S
authors.lastname: Xing
authors.affiliation: Department of Urology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, Hubei, PR China.
authors.forename: Xuepan
authors.initials: X
authors.lastname: Chen
authors.affiliation: Department of Urology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, Hubei, PR China.
authors.forename: Jin
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Urology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, Hubei, PR China.
authors.forename: Sen
authors.initials: S
authors.lastname: Li
authors.affiliation: Department of Urology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, Hubei, PR China.
authors.forename: Youpeng
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Urology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, Hubei, PR China.
authors.forename: Wei
authors.initials: W
authors.lastname: Xiang
authors.affiliation: Department of Urology, Wuhan No.1 Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei, PR China.
authors.forename: Zhineng
authors.initials: Z
authors.lastname: Zhu
authors.affiliation: Department of Chemistry, Connecticut College, 270 Mohegan Avenue, New London, CT, 06320, United States of America.
authors.forename: Cameron
authors.initials: C
authors.lastname: Johnson
authors.affiliation: Department of Urology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, Hubei, PR China.
authors.forename: Zhaohui
authors.initials: Z
authors.lastname: Zhu
mesh_terms: D000368:Aged; D018450:Disease Progression; D058750:Epithelial-Mesenchymal Transition; D005260:Female; D055785:Gene Knockdown Techniques; D006801:Humans; D008297:Male; D036961:Matrix Attachment Region Binding Proteins / Q000235:genetics / Q000378:metabolism*; D008875:Middle Aged; D009362:Neoplasm Metastasis; D015854:Up-Regulation; D001749:Urinary Bladder Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology
chemical_list: D036961:Matrix Attachment Region Binding Proteins; C076189:SATB1 protein, human