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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.

SUBMITTER: Lu YY

PROVIDER: S-EPMC3944050 | biostudies-literature | 2014 Feb

REPOSITORIES: biostudies-literature

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Prometastatic GPCR CD97 is a direct target of tumor suppressor microRNA-126.

Lu Ying Y YY Sweredoski Michael J MJ Huss David D Lansford Rusty R Hess Sonja S Tirrell David A DA

ACS chemical biology 20131125 2

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 ...[more]

PMID: 24274104

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