Skip to main content
eScholarship
Open Access Publications from the University of California

UCSF

UC San Francisco Previously Published Works bannerUCSF

Direct targeting of Sec23a by miR-200s influences cancer cell secretome and promotes metastatic colonization.

  • Author(s): Korpal, Manav
  • Ell, Brian J
  • Buffa, Francesca M
  • Ibrahim, Toni
  • Blanco, Mario A
  • Celià-Terrassa, Toni
  • Mercatali, Laura
  • Khan, Zia
  • Goodarzi, Hani
  • Hua, Yuling
  • Wei, Yong
  • Hu, Guohong
  • Garcia, Benjamin A
  • Ragoussis, Jiannis
  • Amadori, Dino
  • Harris, Adrian L
  • Kang, Yibin
  • et al.

Published Web Location

https://doi.org/10.1038/nm.2401
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.

Many UC-authored scholarly publications are freely available on this site because of the UC's open access policies. Let us know how this access is important for you.

Main Content
Current View