The Secretion of miR-200s by a PKCζ/ADAR2 Signaling Axis Promotes Liver Metastasis in Colorectal Cancer

Thumbnail
View/Open
Issue date
2018
Author
Shelton, Phillip M.
Duran, Angeles
Nakanishi, Yuki
Reina-Campos, Miguel
Kasashima, Hiroaki
Llado, Victoria
Ma, Li
Campos, Alex
García-Olmo, Damián
García-Arranz, Mariano
García-Olmo, Dolores C.
Olmedillas-López, Susana
Caceres, Javier F.
Diaz-Meco, Maria T.
Moscat, Jorge
Suggested citation
Shelton, Phillip M.; Duran, Angeles; Nakanishi, Yuki; Reina-Campos, Miguel; Kasashima, Hiroaki; Llado, Victoria; ... Moscat, Jorge. (2018) . The Secretion of miR-200s by a PKCζ/ADAR2 Signaling Axis Promotes Liver Metastasis in Colorectal Cancer. Cell Reports, 2018, vol. 23, núm. 4, p. 1178-1191. https://doi.org/10.1016/j.celrep.2018.03.118.
Impact

Google Scholar logo  Google Scholar
Share
Export to Mendeley
Metadata
Show full item record
Abstract
Most colorectal cancer (CRC)-related deaths are due to liver metastases. PKCζ 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 PKCζ deficiency. The regulation of the intracellular levels of miR-200 by PKCζ is post-transcriptional and involves their secretion in extracellular vesicles. Here, we identified ADAR2 as a direct substrate of PKCζ in CRC cells. Phosphorylation of ADAR2 regulates its editing activity, which is required to maintain miR-200 steady-state levels, suggesting that the PKCζ/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 PKCζ/ADAR2 axis is a critical regulator of CRC metastases through modulation of miR-200 levels.
URI
http://hdl.handle.net/10459.1/69025
DOI
https://doi.org/10.1016/j.celrep.2018.03.118
Is part of
Cell Reports, 2018, vol. 23, núm. 4, p. 1178-1191
Collections

The following license files are associated with this item:

cc-by-nc-nd, (c) Shelton et al., 2018
Except where otherwise noted, this item's license is described as cc-by-nc-nd, (c) Shelton et al., 2018