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Plos One : Genomic Loss of Tumor Suppressor Mirna-204 Promotes Cancer Cell Migration and Invasion by Activating Akt, Volume 7

By Viglietto, Giuseppe

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Book Id: WPLBN0003938184
Format Type: PDF eBook :
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Reproduction Date: 2015

Title: Plos One : Genomic Loss of Tumor Suppressor Mirna-204 Promotes Cancer Cell Migration and Invasion by Activating Akt, Volume 7  
Author: Viglietto, Giuseppe
Volume: Volume 7
Language: English
Subject: Journals, Science, Medical Science
Collections: Periodicals: Journal and Magazine Collection
Historic
Publication Date:
Publisher: Plos

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Viglietto, G. (n.d.). Plos One : Genomic Loss of Tumor Suppressor Mirna-204 Promotes Cancer Cell Migration and Invasion by Activating Akt, Volume 7. Retrieved from http://netlibrary.net/


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Description : Increasing evidence suggests that chromosomal regions containing microRNAs are functionally important in cancers. Here, we show that genomic loci encoding miR-204 are frequently lost in multiple cancers, including ovarian cancers, pediatric renal tumors, and breast cancers. MiR-204 shows drastically reduced expression in several cancers and acts as a potent tumor suppressor, inhibiting tumor metastasis in vivo when systemically delivered. We demonstrated that miR-204 exerts its function by targeting genes involved in tumorigenesis including brain-derived neurotrophic factor (BDNF), a neurotrophin family member which is known to promote tumor angiogenesis and invasiveness. Analysis of primary tumors shows that increased expression of BDNF or its receptor tropomyosin-related kinase B (TrkB) parallel a markedly reduced expression of miR-204. Our results reveal that loss of miR-204 results in BDNF overexpression and subsequent activation of the small GTPase Rac1 and actin reorganization through the AKT/mTOR signaling pathway leading to cancer cell migration and invasion. These results suggest that microdeletion of genomic loci containing miR-204 is directly linked with the deregulation of key oncogenic pathways that provide crucial stimulus for tumor growth and metastasis. Our findings provide a strong rationale for manipulating miR-204 levels therapeutically to suppress tumor metastasis.

 

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