Characterization of cytoplasmic cyclin D1 as a marker of invasiveness in cancer

Cyclin D1 (Ccnd1) is a proto-oncogen amplified in many different cancers and nuclear accumulation of Ccnd1 is a characteristic of tumor cells. Ccnd1 activates the transcription of a large set of genes involved in cell cycle progress and proliferation. However, Ccnd1 also targets cytoplasmic proteins...

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Autores: Pérez Fusté, Noel, Castelblanco Echavarría, Esmeralda, Felip Nogués, Isidre, Santacana Espasa, Maria, Fernández Hernández, Rita, Gatius Calderó, Sònia, Pedraza González, Neus, Pallares, Judit, Cemeli, Tània, Valls Marsal, Joan, Tarrés Escalona, Marc, Ferrezuelo, Francisco, Dolcet Roca, Xavier, Matias-Guiu, Xavier, Garí Marsol, Eloi
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2016
País:España
Institución:Universitat de Lleida (UdL)
Repositorio:Repositori Obert UdL
OAI Identifier:oai:repositori.udl.cat:10459.1/57224
Acceso en línea:https://doi.org/10.18632/oncotarget.8876
http://hdl.handle.net/10459.1/57224
Access Level:acceso abierto
Palabra clave:Cyclin D1
Tissue array
Cell invasion
Metastasis
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spelling Characterization of cytoplasmic cyclin D1 as a marker of invasiveness in cancerPérez Fusté, NoelCastelblanco Echavarría, EsmeraldaFelip Nogués, IsidreSantacana Espasa, MariaFernández Hernández, RitaGatius Calderó, SòniaPedraza González, NeusPallares, JuditCemeli, TàniaValls Marsal, JoanTarrés Escalona, MarcFerrezuelo, FranciscoDolcet Roca, XavierMatias-Guiu, XavierGarí Marsol, EloiCyclin D1Tissue arrayCell invasionMetastasisCyclin D1 (Ccnd1) is a proto-oncogen amplified in many different cancers and nuclear accumulation of Ccnd1 is a characteristic of tumor cells. Ccnd1 activates the transcription of a large set of genes involved in cell cycle progress and proliferation. However, Ccnd1 also targets cytoplasmic proteins involved in the regulation of cell migration and invasion. In this work, we have analyzed by immunohistochemistry the localization of Ccnd1 in endometrial, breast, prostate and colon carcinomas with different types of invasion. The number of cells displaying membranous or cytoplasmic Ccnd1 was significantly higher in peripheral cells than in inner cells in both collective and pushing invasion patterns of endometrial carcinoma, and in collective invasion pattern of colon carcinoma. Also, the cytoplasmic localization of Ccnd1 was higher when tumors infiltrated as single cells, budding or small clusters of cells. To evaluate cytoplasmic function of cyclin D1, we have built a variant (Ccnd1-CAAX) that remains attached to the cell membrane therefore sequestering this cyclin in the cytoplasm. Tumor cells harboring Ccnd1-CAAX showed high levels of invasiveness and metastatic potential compared to those containing the wild type allele of Ccnd1. However, Ccnd1- CAAX expression did not alter proliferative rates of tumor cells. We hypothesize that the role of Ccnd1 in the cytoplasm is mainly associated with the invasive capability of tumor cells. Moreover, we propose that subcellular localization of Ccnd1 is an interesting guideline to measure cancer outcome.This work was funded by Spanish Ministry of Education and Science (BFU2010-20293/ BMC and BFU2013-42895-P), Catalan Government (SGR-559), and Fondo de Investigaciones Sanitarias (PI10/00604 and PI13/00263). X.M-G was supported by grants 2014SGR138, RD12/0036/0013, and Fundación Asociación Española contra el Cancer. Tumour samples were obtained with the support of Xarxa Catalana de Bancs de Tumors, and Plataforma de Biobancos ISCIII (PT13/0010/0014). NP. Fusté was supported by a contract from “Fundació Alicia Cuello de Merigó”. I. Felip and T. Cemeli were supported by a predoctoral fellowship from FPU-MINECO.Impact Journals2016info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttps://doi.org/10.18632/oncotarget.8876http://hdl.handle.net/10459.1/57224reponame:Repositori Obert UdL instname:Universitat de Lleida (UdL)Inglésinfo:eu-repo/grantAgreement/MICINN//BFU2010-20293info:eu-repo/grantAgreement/MINECO//BFU2013-42895-PReproducció del document publicat a https://doi.org/10.18632/oncotarget.8876Oncotarget, 2016, vol. 7, núm. 19, p. 26979-26991cc-by, (c) Impact Journals, 2016info:eu-repo/semantics/openAccesshttp://creativecommons.org/licenses/by/3.0/es/oai:repositori.udl.cat:10459.1/572242026-06-24T12:42:17Z
dc.title.none.fl_str_mv Characterization of cytoplasmic cyclin D1 as a marker of invasiveness in cancer
title Characterization of cytoplasmic cyclin D1 as a marker of invasiveness in cancer
spellingShingle Characterization of cytoplasmic cyclin D1 as a marker of invasiveness in cancer
Pérez Fusté, Noel
Cyclin D1
Tissue array
Cell invasion
Metastasis
title_short Characterization of cytoplasmic cyclin D1 as a marker of invasiveness in cancer
title_full Characterization of cytoplasmic cyclin D1 as a marker of invasiveness in cancer
title_fullStr Characterization of cytoplasmic cyclin D1 as a marker of invasiveness in cancer
title_full_unstemmed Characterization of cytoplasmic cyclin D1 as a marker of invasiveness in cancer
title_sort Characterization of cytoplasmic cyclin D1 as a marker of invasiveness in cancer
dc.creator.none.fl_str_mv Pérez Fusté, Noel
Castelblanco Echavarría, Esmeralda
Felip Nogués, Isidre
Santacana Espasa, Maria
Fernández Hernández, Rita
Gatius Calderó, Sònia
Pedraza González, Neus
Pallares, Judit
Cemeli, Tània
Valls Marsal, Joan
Tarrés Escalona, Marc
Ferrezuelo, Francisco
Dolcet Roca, Xavier
Matias-Guiu, Xavier
Garí Marsol, Eloi
author Pérez Fusté, Noel
author_facet Pérez Fusté, Noel
Castelblanco Echavarría, Esmeralda
Felip Nogués, Isidre
Santacana Espasa, Maria
Fernández Hernández, Rita
Gatius Calderó, Sònia
Pedraza González, Neus
Pallares, Judit
Cemeli, Tània
Valls Marsal, Joan
Tarrés Escalona, Marc
Ferrezuelo, Francisco
Dolcet Roca, Xavier
Matias-Guiu, Xavier
Garí Marsol, Eloi
author_role author
author2 Castelblanco Echavarría, Esmeralda
Felip Nogués, Isidre
Santacana Espasa, Maria
Fernández Hernández, Rita
Gatius Calderó, Sònia
Pedraza González, Neus
Pallares, Judit
Cemeli, Tània
Valls Marsal, Joan
Tarrés Escalona, Marc
Ferrezuelo, Francisco
Dolcet Roca, Xavier
Matias-Guiu, Xavier
Garí Marsol, Eloi
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Cyclin D1
Tissue array
Cell invasion
Metastasis
topic Cyclin D1
Tissue array
Cell invasion
Metastasis
description Cyclin D1 (Ccnd1) is a proto-oncogen amplified in many different cancers and nuclear accumulation of Ccnd1 is a characteristic of tumor cells. Ccnd1 activates the transcription of a large set of genes involved in cell cycle progress and proliferation. However, Ccnd1 also targets cytoplasmic proteins involved in the regulation of cell migration and invasion. In this work, we have analyzed by immunohistochemistry the localization of Ccnd1 in endometrial, breast, prostate and colon carcinomas with different types of invasion. The number of cells displaying membranous or cytoplasmic Ccnd1 was significantly higher in peripheral cells than in inner cells in both collective and pushing invasion patterns of endometrial carcinoma, and in collective invasion pattern of colon carcinoma. Also, the cytoplasmic localization of Ccnd1 was higher when tumors infiltrated as single cells, budding or small clusters of cells. To evaluate cytoplasmic function of cyclin D1, we have built a variant (Ccnd1-CAAX) that remains attached to the cell membrane therefore sequestering this cyclin in the cytoplasm. Tumor cells harboring Ccnd1-CAAX showed high levels of invasiveness and metastatic potential compared to those containing the wild type allele of Ccnd1. However, Ccnd1- CAAX expression did not alter proliferative rates of tumor cells. We hypothesize that the role of Ccnd1 in the cytoplasm is mainly associated with the invasive capability of tumor cells. Moreover, we propose that subcellular localization of Ccnd1 is an interesting guideline to measure cancer outcome.
publishDate 2016
dc.date.none.fl_str_mv 2016
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/10.18632/oncotarget.8876
http://hdl.handle.net/10459.1/57224
url https://doi.org/10.18632/oncotarget.8876
http://hdl.handle.net/10459.1/57224
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv info:eu-repo/grantAgreement/MICINN//BFU2010-20293
info:eu-repo/grantAgreement/MINECO//BFU2013-42895-P
Reproducció del document publicat a https://doi.org/10.18632/oncotarget.8876
Oncotarget, 2016, vol. 7, núm. 19, p. 26979-26991
dc.rights.none.fl_str_mv cc-by, (c) Impact Journals, 2016
info:eu-repo/semantics/openAccess
http://creativecommons.org/licenses/by/3.0/es/
rights_invalid_str_mv cc-by, (c) Impact Journals, 2016
http://creativecommons.org/licenses/by/3.0/es/
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv Impact Journals
publisher.none.fl_str_mv Impact Journals
dc.source.none.fl_str_mv reponame:Repositori Obert UdL
instname:Universitat de Lleida (UdL)
instname_str Universitat de Lleida (UdL)
reponame_str Repositori Obert UdL
collection Repositori Obert UdL
repository.name.fl_str_mv
repository.mail.fl_str_mv
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