title: Regulation of metastasis of bladder cancer cells through the WNT signaling pathway.
abstract: Bladder cancer (BC) is the most popular malignant urinary cancer, with the highest incidence and mortality of all genitourinary system tumors worldwide. To date, the molecular regulation of the metastasis of BC remains ill defined. Here, we examined the levels of matrix metallopeptidase 9 (MMP9) and nuclear β-catenin in the BC specimen. We used lithium chloride (LiCl) to inhibit cytosol β-catenin phosphorylation and degradation to increase nuclear β-catenin levels in BC cells. We used IWP-2 to enhance cytosol β-catenin phosphorylation and degradation to decrease nuclear β-catenin levels in BC cells. We examined MMP9 levels in these experimental settings by quantitative reverse transcription-PCR (RT-qPCR), Western blot, and ELISA. The cell invasiveness was evaluated by Transwell cell assay. We found significantly higher levels of MMP9 and nuclear β-catenin in human BC specimen with metastasis, compared to those without metastasis. Moreover, a strong correlation was detected between MMP9 and nuclear β-catenin. LiCl significantly increased nuclear β-catenin, resulting in MMP9 activation in BC cells. IWP-2 significantly decreased nuclear β-catenin, resulting in MMP9 inhibition in BC cells. MMP9 regulated cell invasiveness. Together, these data suggest that the WNT signaling pathway regulates metastasis of BC through activation of MMP9. Therapies targeting the WNT signaling pathway may be a promising treatment for BC.
authors.affiliation: Department of Urology, Shanghai First People's Hospital, Shanghai Jiao Tong University, 100 Haining Rd, Shanghai, 200080, China.
authors.forename: Yiheng
authors.initials: Y
authors.lastname: Du
authors.affiliation: Department of Urology, Weifang Hospital of Chinese Traditional Medicine, Weifang, 261041, China.
authors.forename: Yongchuan
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Urology, Shanghai First People's Hospital, Shanghai Jiao Tong University, 100 Haining Rd, Shanghai, 200080, China.
authors.forename: Fei
authors.initials: F
authors.lastname: Zhang
authors.affiliation: Department of Urology, Shanghai First People's Hospital, Shanghai Jiao Tong University, 100 Haining Rd, Shanghai, 200080, China.
authors.forename: Wenbo
authors.initials: W
authors.lastname: Wu
authors.affiliation: Department of Urology, Shanghai First People's Hospital, Shanghai Jiao Tong University, 100 Haining Rd, Shanghai, 200080, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.affiliation: Department of Urology, Shanghai First People's Hospital, Shanghai Jiao Tong University, 100 Haining Rd, Shanghai, 200080, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Li
authors.affiliation: Department of Urology, Shanghai First People's Hospital, Shanghai Jiao Tong University, 100 Haining Rd, Shanghai, 200080, China.
authors.forename: Shujie
authors.initials: S
authors.lastname: Xia
authors.affiliation: Department of Urology, Shanghai First People's Hospital, Shanghai Jiao Tong University, 100 Haining Rd, Shanghai, 200080, China. liuhaitao4@163.com.
authors.forename: Haitao
authors.initials: H
authors.lastname: Liu
mesh_terms: D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D018021:Lithium Chloride / Q000008:administration & dosage; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis* / Q000235:genetics; D009362:Neoplasm Metastasis; D010766:Phosphorylation / Q000187:drug effects; D059748:Proteolysis / Q000187:drug effects; D001749:Urinary Bladder Neoplasms / Q000235:genetics* / Q000473:pathology; D060449:Wnt Signaling Pathway / Q000187:drug effects*; D051176:beta Catenin / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D051176:beta Catenin; C579270:MMP9 protein, human; D020780:Matrix Metalloproteinase 9; D018021:Lithium Chloride
keywords: Bladder cancer (BC); MMP9; WNT signaling; β-Catenin