|MicroRNA-374a activates Wnt/β-catenin signaling to promote breast cancer metastasis.|
|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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|Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2013-01-16|
|Title: The Journal of clinical investigation Volume: 123 ISSN: 1558-8238 ISO Abbreviation: J. Clin. Invest. Publication Date: 2013 Feb|
|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|
|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.|
|Data Bank Information|
Bank Name/Acc. No.:
|APA/MLA Format Download EndNote Download BibTex|
Adaptor Proteins, Signal Transducing
Breast Neoplasms / genetics*, metabolism*, pathology, secondary
Cell Line, Tumor
Lung Neoplasms / secondary
Mice, Inbred BALB C
MicroRNAs / genetics*
PTEN Phosphohydrolase / metabolism
Proto-Oncogene Proteins / metabolism
RNA, Neoplasm / genetics
Repressor Proteins / metabolism
Wnt Proteins / metabolism
Wnt Signaling Pathway*
beta Catenin / metabolism*
|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 188.8.131.52/PTEN protein, human; EC 184.108.40.206/PTEN Phosphohydrolase|
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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