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

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dc.contributor.authorShelton, Phillip M.
dc.contributor.authorDuran, Angeles
dc.contributor.authorNakanishi, Yuki
dc.contributor.authorReina-Campos, Miguel
dc.contributor.authorKasashima, Hiroaki
dc.contributor.authorLlado, Victoria
dc.contributor.authorMa, Li
dc.contributor.authorCampos, Alex
dc.contributor.authorGarcía-Olmo, Damián
dc.contributor.authorGarcía-Arranz, Mariano
dc.contributor.authorGarcía-Olmo, Dolores C.
dc.contributor.authorOlmedillas-López, Susana
dc.contributor.authorCaceres, Javier F.
dc.contributor.authorDiaz-Meco, Maria T.
dc.contributor.authorMoscat, Jorge
dc.date.accessioned2020-06-16T10:43:37Z
dc.date.available2020-06-16T10:43:37Z
dc.date.issued2018
dc.description.abstractMost 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.ca_ES
dc.description.sponsorshipResearch was supported by grants from the NIH ( R01DK108743 , R01CA172025 , and R01CA207177 to J.M.; R01CA192642 and R01CA218254 to M.T.D.-M.).ca_ES
dc.identifier.doihttps://doi.org/10.1016/j.celrep.2018.03.118
dc.identifier.issn2211-1247
dc.identifier.urihttp://hdl.handle.net/10459.1/69025
dc.language.isoengca_ES
dc.publisherElsevierca_ES
dc.relation.isformatofReproducció del document publicat a https://doi.org/10.1016/j.celrep.2018.03.118ca_ES
dc.relation.ispartofCell Reports, 2018, vol. 23, núm. 4, p. 1178-1191ca_ES
dc.rightscc-by-nc-nd, (c) Shelton et al., 2018ca_ES
dc.rights.accessRightsinfo:eu-repo/semantics/openAccessca_ES
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/*
dc.subjectPRKCZca_ES
dc.subjectAtypical PKCca_ES
dc.subjectADAR2ca_ES
dc.subjectColorectal cancerca_ES
dc.subjectMetastasisca_ES
dc.titleThe Secretion of miR-200s by a PKCζ/ADAR2 Signaling Axis Promotes Liver Metastasis in Colorectal Cancerca_ES
dc.typeinfo:eu-repo/semantics/articleca_ES
dc.type.versioninfo:eu-repo/semantics/publishedVersionca_ES
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