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Prometastatic GPCR CD97 Is a Direct Target of Tumor Suppressor microRNA-126

Lu, Ying Y. and Sweredoski, Michael J. and Huss, David and Lansford, Rusty and Hess, Sonja and Tirrell, David A. (2014) Prometastatic GPCR CD97 Is a Direct Target of Tumor Suppressor microRNA-126. ACS Chemical Biology, 9 (2). pp. 334-338. ISSN 1554-8929. PMCID PMC3944050.

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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.

Item Type:Article
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URLURL TypeDescription CentralArticle
Sweredoski, Michael J.0000-0003-0878-3831
Lansford, Rusty0000-0002-2159-3699
Hess, Sonja0000-0002-5904-9816
Tirrell, David A.0000-0003-3175-4596
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.
Funding AgencyGrant Number
NIHR01 GM062523
Caltech Beckman InstituteUNSPECIFIED
Gordon and Betty Moore FoundationGBMF775
Issue or Number:2
PubMed Central ID:PMC3944050
Record Number:CaltechAUTHORS:20131204-105211879
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Official Citation:Prometastatic GPCR CD97 Is a Direct Target of Tumor Suppressor microRNA-126 Ying Y. Lu, Michael J. Sweredoski, David Huss, Rusty Lansford, Sonja Hess, and David A. Tirrell ACS Chemical Biology 2014 9 (2), 334-338
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:42825
Deposited By: Tony Diaz
Deposited On:04 Dec 2013 21:40
Last Modified:03 Oct 2019 06:02

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