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PLoS One. 2013 Nov 11;8(11):e80300. doi: 10.1371/journal.pone.0080300. eCollection 2013.

MiR-424/503-mediated Rictor upregulation promotes tumor progression.

Author information

1
Department of Oncogene Research, Research Institute for Microbial Diseases, Osaka University, Suita, Osaka, Japan.

Abstract

mTOR complex 2 (mTORC2) signaling is upregulated in multiple types of human cancer, but the molecular mechanisms underlying its activation and regulation remain elusive. Here, we show that microRNA-mediated upregulation of Rictor, an mTORC2-specific component, contributes to tumor progression. Rictor is upregulated via the repression of the miR-424/503 cluster in human prostate and colon cancer cell lines that harbor c-Src upregulation and in Src-transformed cells. The tumorigenicity and invasive activity of these cells were suppressed by re-expression of miR-424/503. Rictor upregulation promotes formation of mTORC2 and induces activation of mTORC2, resulting in promotion of tumor growth and invasion. Furthermore, downregulation of miR-424/503 is associated with Rictor upregulation in colon cancer tissues. These findings suggest that the miR-424/503-Rictor pathway plays a crucial role in tumor progression.

PMID:
24244675
PMCID:
PMC3823661
DOI:
10.1371/journal.pone.0080300
[Indexed for MEDLINE]
Free PMC Article

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