%0 Journal Article %J Nature Medicine %D 2011 %T Direct targeting of Sec23a by miR-200s influences cancer cell secretome and promotes metastatic colonization %A Korpal, Manav %A Ell, Brian J. %A Buffa, Francesca M. %A Ibrahim, Toni %A Blanco, Mario A. %A Celià-Terrassa, Toni %A Mercatali, Laura %A Zia Khan %A Goodarzi, Hani %A Hua, Yuling %A Wei, Yong %A Hu, Guohong %A Garcia, Benjamin A. %A Ragoussis, Jiannis %A Amadori, Dino %A Harris, Adrian L. %A Kang, Yibin %X Although the role of miR-200s in regulating E-cadherin expression and epithelial-to-mesenchymal transition is well established, their influence on metastatic colonization remains controversial. Here we have used clinical and experimental models of breast cancer metastasis to discover a pro-metastatic role of miR-200s that goes beyond their regulation of E-cadherin and epithelial phenotype. Overexpression of miR-200s is associated with increased risk of metastasis in breast cancer and promotes metastatic colonization in mouse models, phenotypes that cannot be recapitulated by E-cadherin expression alone. Genomic and proteomic analyses revealed global shifts in gene expression upon miR-200 overexpression toward that of highly metastatic cells. miR-200s promote metastatic colonization partly through direct targeting of Sec23a, which mediates secretion of metastasis-suppressive proteins, including Igfbp4 and Tinagl1, as validated by functional and clinical correlation studies. Overall, these findings suggest a pleiotropic role of miR-200s in promoting metastatic colonization by influencing E-cadherin–dependent epithelial traits and Sec23a-mediated tumor cell secretome.View full text %B Nature Medicine %V 17 %P 1101 - 1108 %8 2011/09// %@ 1078-8956 %G eng %U http://www.nature.com/nm/journal/v17/n9/abs/nm.2401.html %N 9 %! Nat Med