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Wnt7a activates canonical Wnt signaling, promotes bladder cancer cell invasion, and is suppressed by miR-370-3p

文献类型：期刊论文

作者Huang, Xiaojing1,2; Zhu, Hongwen3; Gao, Zemin1,2; Li, Junzun1,2; Zhuang, Junlong5; Dong, Yu3,6; Shen, Bing7; Li, Meiqian1,2; Zhou, Hu3; Guo, Hongqian5
刊名JOURNAL OF BIOLOGICAL CHEMISTRY
出版日期2018-05-04
卷号293期号:18页码:6693-6706
关键词Wnt signaling cancer biology invasion mass spectrometry (MS) microRNA (miRNA) metalloprotease bladder cancer miR-370-3p MMP10 Wnt7a
ISSN号0021-9258
DOI10.1074/jbc.RA118.001689
文献子类Article
英文摘要Once urinary bladder cancer (UBC) develops into muscle-invasive bladder cancer, its mortality rate increases dramatically. However, the molecular mechanisms of UBC invasion and metastasis remain largely unknown. Herein, using 5637 UBC cells, we generated two sublines with low (5637 NMI) and high (5637 HMI) invasive capabilities. Mass spectrum analyses revealed that the Wnt family protein Wnt7a is more highly expressed in 5637 HMI cells than in 5637 NMI cells. We also found that increased Wnt7a expression is associated with UBC metastasis and predicted worse clinical outcome in UBC patients. Wnt7a depletion in 5637 HMI and T24 cells reduced UBC cell invasion and decreased levels of active -catenin and its downstream target genes involved in the epithelial-to-mesenchymal transition (EMT) and extracellular matrix (ECM) degradation. Consistently, treating 5637 NMI and J82 cells with recombinant Wnt7a induced cell invasion, EMT, and expression of ECM degradation-associated genes. Moreover, TOP/FOPflash luciferase assays indicated that Wnt7a activated canonical -catenin signaling in UBC cells, and increased Wnt7a expression was associated with nuclear -catenin in UBC samples. Wnt7a ablation suppressed matrix metalloproteinase 10 (MMP10) expression, and Wnt7a overexpression increased MMP10 promoter activity through two TCF/LEF promoter sites, confirming that Wnt7a-mediated MMP10 activation is mediated by the canonical Wnt/-catenin pathway. Of note, the microRNA miR-370-3p directly repressed Wnt7a expression and thereby suppressed UBC cell invasion, which was partially restored by Wnt7a overexpression. Our results have identified an miR-370-3p/Wnt7a axis that controls UBC invasion through canonical Wnt/-catenin signaling, which may offer prognostic and therapeutic opportunities.
WOS关键词OVARIAN-CANCER ; BETA-CATENIN ; LUNG-CANCER ; MOLECULAR CHARACTERIZATION ; EPIGENETIC INACTIVATION ; UP-REGULATION ; TUMOR-GROWTH ; EXPRESSION ; PATHWAY ; DIFFERENTIATION
资助项目National Natural Science Foundation of China[81372168] ; National Natural Science Foundation of China[81572519] ; National Natural Science Foundation of China[81672873] ; National Natural Science Foundation of China[81771890] ; Open Foundation of State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University[KF-GN-201602] ; State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences[SIMM1705KF-02] ; State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences[SIMM1705KF-06] ; One Hundred Talent Program of Chinese Academy of Sciences[00000000]
WOS研究方向Biochemistry & Molecular Biology
语种英语
WOS记录号WOS:000431487300007
出版者AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
源URL[http://119.78.100.183/handle/2S10ELR8/279768]  
专题分子影像中心（筹）
中科院受体结构与功能重点实验室
新药研究国家重点实验室
通讯作者Yan, Jun
作者单位1.Nanjing Univ, Model Anim Res Ctr, MOE Key Lab Model Anim Dis Study, Nanjing, Jiangsu 210061, Peoples R China;
2.Nanjing Univ, Model Anim Res Ctr, State Key Lab Pharmaceut Biotechnol, Nanjing, Jiangsu 210061, Peoples R China;
3.Chinese Acad Sci, Shanghai Inst Mat Med, Shanghai 201203, Peoples R China;
4.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China;
5.Nanjing Univ, Med Sch, Nanjing Drum Tower Hosp, Dept Urol, Nanjing 210008, Jiangsu, Peoples R China;
6.Shanghai Univ, Shanghai 200444, Peoples R China;
7.Shanghai Jiao Tong Univ, Shanghai Gen Hosp, Dept Urol, Shanghai 200080, Peoples R China
推荐引用方式
GB/T 7714		 Huang, Xiaojing,Zhu, Hongwen,Gao, Zemin,et al. Wnt7a activates canonical Wnt signaling, promotes bladder cancer cell invasion, and is suppressed by miR-370-3p[J]. JOURNAL OF BIOLOGICAL CHEMISTRY,2018,293(18):6693-6706.
APA Huang, Xiaojing.,Zhu, Hongwen.,Gao, Zemin.,Li, Junzun.,Zhuang, Junlong.,...&Yan, Jun.(2018).Wnt7a activates canonical Wnt signaling, promotes bladder cancer cell invasion, and is suppressed by miR-370-3p.JOURNAL OF BIOLOGICAL CHEMISTRY,293(18),6693-6706.
MLA Huang, Xiaojing,et al."Wnt7a activates canonical Wnt signaling, promotes bladder cancer cell invasion, and is suppressed by miR-370-3p".JOURNAL OF BIOLOGICAL CHEMISTRY 293.18(2018):6693-6706.

入库方式： OAI收割

来源：上海药物研究所

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