Document Detail

MicroRNA-374a activates Wnt/β-catenin signaling to promote breast cancer metastasis.
MedLine Citation:
PMID:  23321667     Owner:  NLM     Status:  MEDLINE    
Tumor metastasis involves a series of biological steps during which the tumor cells acquire the ability to invade surrounding tissues and survive outside the original tumor site. During the early stages, the cancer cells undergo an epithelial-mesenchymal transition (EMT). Wnt/β-catenin signaling is known to drive EMT and metastasis. Here we report that Wnt/β-catenin signaling is hyperactivated in metastatic breast cancer cells that express microRNA 374a (miR-374a). In breast cancer cell lines, ectopic overexpression of miR-374a promoted EMT and metastasis both in vitro and in vivo. Furthermore, miR-374a directly targeted and suppressed multiple negative regulators of the Wnt/β-catenin signaling cascade, including WIF1, PTEN, and WNT5A. Notably, miR-374a was markedly upregulated in primary tumor samples from patients with distant metastases and was associated with poor metastasis-free survival. These results demonstrate that miR-374a maintains constitutively activated Wnt/β-catenin signaling and may represent a therapeutic target for early metastatic breast cancer.
Junchao Cai; Hongyu Guan; Lishan Fang; Yi Yang; Xun Zhu; Jie Yuan; Jueheng Wu; Mengfeng Li
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2013-01-16
Journal Detail:
Title:  The Journal of clinical investigation     Volume:  123     ISSN:  1558-8238     ISO Abbreviation:  J. Clin. Invest.     Publication Date:  2013 Feb 
Date Detail:
Created Date:  2013-04-19     Completed Date:  2013-05-13     Revised Date:  2013-07-11    
Medline Journal Info:
Nlm Unique ID:  7802877     Medline TA:  J Clin Invest     Country:  United States    
Other Details:
Languages:  eng     Pagination:  566-79     Citation Subset:  AIM; IM    
Key Laboratory of Tropical Disease Control, Sun Yat-sen University, Ministry of Education, Guangzhou, Guangdong, China.
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MeSH Terms
Adaptor Proteins, Signal Transducing / metabolism
Base Sequence
Breast Neoplasms / genetics*,  metabolism*,  pathology,  secondary
Cell Line, Tumor
Epithelial-Mesenchymal Transition
Lung Neoplasms / secondary
MCF-7 Cells
Mice, Inbred BALB C
Mice, Nude
MicroRNAs / genetics*
Middle Aged
Neoplasm Invasiveness
Neoplasm Transplantation
PTEN Phosphohydrolase / metabolism
Proto-Oncogene Proteins / metabolism
RNA, Neoplasm / genetics
Repressor Proteins / metabolism
Transplantation, Heterologous
Wnt Proteins / metabolism
Wnt Signaling Pathway*
beta Catenin / metabolism*
Reg. No./Substance:
0/Adaptor Proteins, Signal Transducing; 0/CTNNB1 protein, human; 0/MicroRNAs; 0/Proto-Oncogene Proteins; 0/RNA, Neoplasm; 0/Repressor Proteins; 0/WIF1 protein, human; 0/WNT5A protein, human; 0/Wnt Proteins; 0/beta Catenin; EC protein, human; EC Phosphohydrolase

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