@article{148b4311d55547bdab809551cd17fa2a,
title = "Direct targeting of Sec23a by miR-200s influences cancer cell secretome and promotes metastatic colonization",
abstract = "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.",
author = "Manav Korpal and Ell, {Brian J.} and Buffa, {Francesca M.} and Toni Ibrahim and Blanco, {Mario A.} and Toni Celi{\`a}-Terrassa and Laura Mercatali and Zia Khan and Hani Goodarzi and Yuling Hua and Yong Wei and Guohong Hu and Garcia, {Benjamin A.} and Jiannis Ragoussis and Dino Amadori and Harris, {Adrian L.} and Yibin Kang",
note = "Funding Information: We thank S. Kyne at the mass spectrometry core facility, D. Storton and J. Buckles at the microarray core facility, and E. Williams at the electron microscopy facility of Princeton University for expert technical advice and support, N. Sethi for insightful discussions and blinded verification of tumor counts, S.J. Parkinson for technical advice, and K. Socha for colony counting. We also thank E. Williams (Monash Institute of Medical Research) and F. Miller (Barbara Ann Karmanos Cancer Institute) for the TSU-PR1 and 4T1 cell line series, respectively. Y.K. is a Champalimaud Investigator and a Department of Defense Era of Hope Scholar Award recipient. This research was supported by grants from the US National Institutes of Health (1R01-CA141062) and the Brewster Foundation to Y.K. and from Cancer Research UK, Oxford NHS Biomedical Research Centre and Friends of Kennington Cancer Fund to A.L.H. M.K. and Y.H. are recipients of US Department of Defense predoctoral fellowships.",
year = "2011",
month = sep,
doi = "10.1038/nm.2401",
language = "English (US)",
volume = "17",
pages = "1101--1109",
journal = "Nature Medicine",
issn = "1078-8956",
publisher = "Nature Publishing Group",
number = "9",
}