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

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...

Descripción completa

Detalles Bibliográficos
Autores: 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
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2018
País:España
Institución:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repositorio:Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:oai:recercat.cat:10459.1/69025
Acceso en línea:https://doi.org/10.1016/j.celrep.2018.03.118
http://hdl.handle.net/10459.1/69025
Access Level:acceso abierto
Palabra clave:PRKCZ
Atypical PKC
ADAR2
Colorectal cancer
Metastasis
id ES_9fde414bdcbfeebdcb2daf606ffe9adc
oai_identifier_str oai:recercat.cat:10459.1/69025
network_acronym_str ES
network_name_str España
repository_id_str
spelling The Secretion of miR-200s by a PKCζ/ADAR2 Signaling Axis Promotes Liver Metastasis in Colorectal CancerShelton, Phillip M.Duran, AngelesNakanishi, YukiReina-Campos, MiguelKasashima, HiroakiLlado, VictoriaMa, LiCampos, AlexGarcía-Olmo, DamiánGarcía-Arranz, MarianoGarcía-Olmo, Dolores C.Olmedillas-López, SusanaCaceres, Javier F.Diaz-Meco, Maria T.Moscat, JorgePRKCZAtypical PKCADAR2Colorectal cancerMetastasisMost 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.Research was supported by grants from the NIH ( R01DK108743 , R01CA172025 , and R01CA207177 to J.M.; R01CA192642 and R01CA218254 to M.T.D.-M.).Elsevier202020202018info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttps://doi.org/10.1016/j.celrep.2018.03.118http://hdl.handle.net/10459.1/69025http://hdl.handle.net/10459.1/69025reponame:Recercat. Dipósit de la Recerca de Catalunyainstname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)InglésReproducció del document publicat a https://doi.org/10.1016/j.celrep.2018.03.118Cell Reports, 2018, vol. 23, núm. 4, p. 1178-1191cc-by-nc-nd, (c) Shelton et al., 2018info:eu-repo/semantics/openAccesshttp://creativecommons.org/licenses/by-nc-nd/4.0/oai:recercat.cat:10459.1/690252026-05-29T05:05:01Z
dc.title.none.fl_str_mv The Secretion of miR-200s by a PKCζ/ADAR2 Signaling Axis Promotes Liver Metastasis in Colorectal Cancer
title The Secretion of miR-200s by a PKCζ/ADAR2 Signaling Axis Promotes Liver Metastasis in Colorectal Cancer
spellingShingle The Secretion of miR-200s by a PKCζ/ADAR2 Signaling Axis Promotes Liver Metastasis in Colorectal Cancer
Shelton, Phillip M.
PRKCZ
Atypical PKC
ADAR2
Colorectal cancer
Metastasis
title_short The Secretion of miR-200s by a PKCζ/ADAR2 Signaling Axis Promotes Liver Metastasis in Colorectal Cancer
title_full The Secretion of miR-200s by a PKCζ/ADAR2 Signaling Axis Promotes Liver Metastasis in Colorectal Cancer
title_fullStr The Secretion of miR-200s by a PKCζ/ADAR2 Signaling Axis Promotes Liver Metastasis in Colorectal Cancer
title_full_unstemmed The Secretion of miR-200s by a PKCζ/ADAR2 Signaling Axis Promotes Liver Metastasis in Colorectal Cancer
title_sort The Secretion of miR-200s by a PKCζ/ADAR2 Signaling Axis Promotes Liver Metastasis in Colorectal Cancer
dc.creator.none.fl_str_mv 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
author Shelton, Phillip M.
author_facet 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
author_role author
author2 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
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv PRKCZ
Atypical PKC
ADAR2
Colorectal cancer
Metastasis
topic PRKCZ
Atypical PKC
ADAR2
Colorectal cancer
Metastasis
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.
publishDate 2018
dc.date.none.fl_str_mv 2018
2020
2020
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://doi.org/10.1016/j.celrep.2018.03.118
http://hdl.handle.net/10459.1/69025
http://hdl.handle.net/10459.1/69025
url https://doi.org/10.1016/j.celrep.2018.03.118
http://hdl.handle.net/10459.1/69025
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Reproducció del document publicat a https://doi.org/10.1016/j.celrep.2018.03.118
Cell Reports, 2018, vol. 23, núm. 4, p. 1178-1191
dc.rights.none.fl_str_mv cc-by-nc-nd, (c) Shelton et al., 2018
info:eu-repo/semantics/openAccess
http://creativecommons.org/licenses/by-nc-nd/4.0/
rights_invalid_str_mv cc-by-nc-nd, (c) Shelton et al., 2018
http://creativecommons.org/licenses/by-nc-nd/4.0/
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv Elsevier
publisher.none.fl_str_mv Elsevier
dc.source.none.fl_str_mv reponame:Recercat. Dipósit de la Recerca de Catalunya
instname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
instname_str Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
reponame_str Recercat. Dipósit de la Recerca de Catalunya
collection Recercat. Dipósit de la Recerca de Catalunya
repository.name.fl_str_mv
repository.mail.fl_str_mv
_version_ 1869414964272300032
score 15.81155

Similares en LA Referencia