MicroRNA-200c: A Novel Way to Attack Breast Cancer Metastases by Restoring the Epithelial Phenotype
Abstract
Our most significant findings over the duration of this idea award "MicroRNA-200c: A Novel Way to Attack Breast Cancer Metastases by Restoring the Epithelial Phenotype" grant are evident in our 8 publications (3 of which are reviews). The miR- 200 family is the most differentially expressed miRNA in ER+ versus triple negative breast cancer (TNBC) cell lines and clinical samples. We find that miR-200 affects multiple aspects of epithelial to mesenchymal transition (EMT). Restoration of miR-200c to TNBC decreases migration and invasion and represses a whole program of nonepithelial genes normally expressed in cells of mesenchymal or neuronal origin. We made the novel observation that restoration of miR-200c enhances sensitivity to anoikis (cell death induced by detachment) and that this is mediated by direct targeting of TrkB. This year we published that one of the ligands of the TrkB receptor, NTF3 is also a target of miR-200c and the loss of miR-200cin TNBC sets up an inappropriate autocrine loop that provides a signal that allows TNBC cells to survive unattached and thereby be able to metastasize. Lastly, in as yet unpublished work we induce miR-200c in TNBC cells in the blood stream to determine if fewer cells are able to survive and form metastases in the lungs of mice.
Document Details
- Document Type
- Technical Report
- Publication Date
- Dec 01, 2012
- Accession Number
- ADA580871
Entities
People
- Jennifer K Richer
Organizations
- University of Colorado Boulder