MiR-424/503-mediated Rictor upregulation promotes tumor progression.
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. Ricto...
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| Main Authors: | , , , , , , , , , , , |
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| Format: | article |
| Language: | EN |
| Published: |
Public Library of Science (PLoS)
2013
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| Subjects: | |
| Online Access: | https://doaj.org/article/8670d7cb97c449a39cb6314a7ccd8123 |
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| Summary: | 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. |
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