Prometastatic GPCR CD97 Is a Direct Target of Tumor Suppressor microRNA-126
Abstract
Tumor suppressor microRNA-126 (miR-126) is often down-regulated in cancer cells, and its overexpression is found to inhibit cancer metastasis. To elucidate the mechanism of tumor suppression by miR-126, we analyzed the proteomic response to miR-126 overexpression in the human metastatic breast cancer cell line MDA-MB-231. To acquire quantitative, time-resolved information, we combined two complementary proteomic methods, BONCAT and SILAC. We discovered a new direct target of miR-126: CD97, a pro-metastatic G-protein-coupled receptor (GPCR) that has been reported to promote tumor cell invasion, endothelial cell migration, and tumor angiogenesis. This discovery establishes a link between down-regulation of miR-126 and overexpression of CD97 in cancer and provides new mechanistic insight into the role of miR-126 in inhibiting both cell-autonomous and non-cell-autonomous cancer progression.
Additional Information
© 2013 American Chemical Society. Received: September 12, 2013; Accepted: November 12, 2013. Publication Date (Web): November 25, 2013. We thank R. Graham, A. Moradian, and G. Smith at the Proteome Exploration Laboratory of the Beckman Institute at Caltech for assistance with proteomic studies. We thank K. Fang, K. Yuet, and L. Dooling for cloning advice and R. Diamond for assistance with flow cytometry. This work was supported by National Institutes of Health grant NIH R01 GM062523. The Proteome Exploration Laboratory is supported by the Caltech Beckman Institute and by the Gordon and Betty Moore Foundation through Grant GBMF775.Attached Files
Accepted Version - nihms544452.pdf
Supplemental Material - cb400704n_si_001.pdf
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Additional details
- PMCID
- PMC3944050
- Eprint ID
- 42825
- Resolver ID
- CaltechAUTHORS:20131204-105211879
- R01 GM062523
- NIH
- Caltech Beckman Institute
- GBMF775
- Gordon and Betty Moore Foundation
- Created
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2013-12-04Created from EPrint's datestamp field
- Updated
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2021-11-10Created from EPrint's last_modified field