| First Author | Shelton PM | Year | 2018 |
| Journal | Cell Rep | Volume | 23 |
| Issue | 4 | Pages | 1178-1191 |
| PubMed ID | 29694894 | Mgi Jnum | J:270865 |
| Mgi Id | MGI:6278809 | Doi | 10.1016/j.celrep.2018.03.118 |
| Citation | Shelton PM, et al. (2018) The Secretion of miR-200s by a PKCzeta/ADAR2 Signaling Axis Promotes Liver Metastasis in Colorectal Cancer. Cell Rep 23(4):1178-1191 |
| abstractText | Most colorectal cancer (CRC)-related deaths are due to liver metastases. PKCzeta is a tumor suppressor in CRC with reduced expression in metastasis. Given the importance of microRNAs (miRNAs) in regulating cellular plasticity, we performed an unbiased screening and identified the miR-200 family as the most relevant miRNAs downregulated by PKCzeta deficiency. The regulation of the intracellular levels of miR-200 by PKCzeta is post-transcriptional and involves their secretion in extracellular vesicles. Here, we identified ADAR2 as a direct substrate of PKCzeta in CRC cells. Phosphorylation of ADAR2 regulates its editing activity, which is required to maintain miR-200 steady-state levels, suggesting that the PKCzeta/ADAR2 axis regulates miR-200 secretion through RNA editing. Loss of this axis results in epithelial-to-mesenchymal transition (EMT) and increased liver metastases, which can be inhibited in vivo by blocking miR-200 release. Therefore, the PKCzeta/ADAR2 axis is a critical regulator of CRC metastases through modulation of miR-200 levels. |
