dc.contributor.author |
Shelton, Phillip M. |
dc.contributor.author |
Duran, Angeles |
dc.contributor.author |
Nakanishi, Yuki |
dc.contributor.author |
Reina-Campos, Miguel |
dc.contributor.author |
Kasashima, Hiroaki |
dc.contributor.author |
Llado, Victoria |
dc.contributor.author |
Ma, Li |
dc.contributor.author |
Campos, Alex |
dc.contributor.author |
García-Olmo, Damián |
dc.contributor.author |
García-Arranz, Mariano |
dc.contributor.author |
García-Olmo, Dolores C. |
dc.contributor.author |
Olmedillas-López, Susana |
dc.contributor.author |
Caceres, Javier F. |
dc.contributor.author |
Diaz-Meco, Maria T. |
dc.contributor.author |
Moscat, Jorge |
dc.date |
2020-06-16T10:43:37Z |
dc.date |
2020-06-16T10:43:37Z |
dc.date |
2018 |
dc.identifier |
2211-1247 |
dc.identifier |
http://hdl.handle.net/10459.1/69025 |
dc.identifier |
https://doi.org/10.1016/j.celrep.2018.03.118 |
dc.identifier.uri |
http://hdl.handle.net/10459.1/69025 |
dc.description |
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. |
dc.description |
Research was supported by grants from the NIH ( R01DK108743 , R01CA172025 , and R01CA207177 to J.M.; R01CA192642 and R01CA218254 to M.T.D.-M.). |
dc.language |
eng |
dc.publisher |
Elsevier |
dc.relation |
Reproducció del document publicat a https://doi.org/10.1016/j.celrep.2018.03.118 |
dc.relation |
Cell Reports, 2018, vol. 23, núm. 4, p. 1178-1191 |
dc.rights |
cc-by-nc-nd, (c) Shelton et al., 2018 |
dc.rights |
http://creativecommons.org/licenses/by-nc-nd/4.0/ |
dc.rights |
info:eu-repo/semantics/openAccess |
dc.subject |
PRKCZ |
dc.subject |
Atypical PKC |
dc.subject |
ADAR2 |
dc.subject |
Colorectal cancer |
dc.subject |
Metastasis |
dc.title |
The Secretion of miR-200s by a PKCζ/ADAR2 Signaling Axis Promotes Liver Metastasis in Colorectal Cancer |
dc.type |
info:eu-repo/semantics/article |
dc.type |
info:eu-repo/semantics/publishedVersion |