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Cytoplasmic cyclin D1 regulates cell invasion and metastasis through the phosphorylation of paxillin

Cyclin D1 (Ccnd1) together with its binding partner Cdk4 act as a transcriptional regulator to control cell proliferation and migration, and abnormal Ccnd1·Cdk4 expression promotes tumour growth and metastasis. While different nuclear Ccnd1·Cdk4 targets participating in cell proliferation and tissue...

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Autores principales: Fusté, Noel P., Fernández-Hernández, Rita, Cemeli, Tània, Mirantes, Cristina, Pedraza, Neus, Rafel, Marta, Torres-Rosell, Jordi, Colomina, Neus, Ferrezuelo, Francisco, Dolcet, Xavier, Garí, Eloi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4873647/
https://www.ncbi.nlm.nih.gov/pubmed/27181366
http://dx.doi.org/10.1038/ncomms11581
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author Fusté, Noel P.
Fernández-Hernández, Rita
Cemeli, Tània
Mirantes, Cristina
Pedraza, Neus
Rafel, Marta
Torres-Rosell, Jordi
Colomina, Neus
Ferrezuelo, Francisco
Dolcet, Xavier
Garí, Eloi
author_facet Fusté, Noel P.
Fernández-Hernández, Rita
Cemeli, Tània
Mirantes, Cristina
Pedraza, Neus
Rafel, Marta
Torres-Rosell, Jordi
Colomina, Neus
Ferrezuelo, Francisco
Dolcet, Xavier
Garí, Eloi
author_sort Fusté, Noel P.
collection PubMed
description Cyclin D1 (Ccnd1) together with its binding partner Cdk4 act as a transcriptional regulator to control cell proliferation and migration, and abnormal Ccnd1·Cdk4 expression promotes tumour growth and metastasis. While different nuclear Ccnd1·Cdk4 targets participating in cell proliferation and tissue development have been identified, little is known about how Ccnd1·Cdk4 controls cell adherence and invasion. Here, we show that the focal adhesion component paxillin is a cytoplasmic substrate of Ccnd1·Cdk4. This complex phosphorylates a fraction of paxillin specifically associated to the cell membrane, and promotes Rac1 activation, thereby triggering membrane ruffling and cell invasion in both normal fibroblasts and tumour cells. Our results demonstrate that localization of Ccnd1·Cdk4 to the cytoplasm does not simply act to restrain cell proliferation, but constitutes a functionally relevant mechanism operating under normal and pathological conditions to control cell adhesion, migration and metastasis through activation of a Ccnd1·Cdk4-paxillin-Rac1 axis.
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spelling pubmed-48736472016-06-02 Cytoplasmic cyclin D1 regulates cell invasion and metastasis through the phosphorylation of paxillin Fusté, Noel P. Fernández-Hernández, Rita Cemeli, Tània Mirantes, Cristina Pedraza, Neus Rafel, Marta Torres-Rosell, Jordi Colomina, Neus Ferrezuelo, Francisco Dolcet, Xavier Garí, Eloi Nat Commun Article Cyclin D1 (Ccnd1) together with its binding partner Cdk4 act as a transcriptional regulator to control cell proliferation and migration, and abnormal Ccnd1·Cdk4 expression promotes tumour growth and metastasis. While different nuclear Ccnd1·Cdk4 targets participating in cell proliferation and tissue development have been identified, little is known about how Ccnd1·Cdk4 controls cell adherence and invasion. Here, we show that the focal adhesion component paxillin is a cytoplasmic substrate of Ccnd1·Cdk4. This complex phosphorylates a fraction of paxillin specifically associated to the cell membrane, and promotes Rac1 activation, thereby triggering membrane ruffling and cell invasion in both normal fibroblasts and tumour cells. Our results demonstrate that localization of Ccnd1·Cdk4 to the cytoplasm does not simply act to restrain cell proliferation, but constitutes a functionally relevant mechanism operating under normal and pathological conditions to control cell adhesion, migration and metastasis through activation of a Ccnd1·Cdk4-paxillin-Rac1 axis. Nature Publishing Group 2016-05-16 /pmc/articles/PMC4873647/ /pubmed/27181366 http://dx.doi.org/10.1038/ncomms11581 Text en Copyright © 2016, Nature Publishing Group, a division of Macmillan Publishers Limited. All Rights Reserved. http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
spellingShingle Article
Fusté, Noel P.
Fernández-Hernández, Rita
Cemeli, Tània
Mirantes, Cristina
Pedraza, Neus
Rafel, Marta
Torres-Rosell, Jordi
Colomina, Neus
Ferrezuelo, Francisco
Dolcet, Xavier
Garí, Eloi
Cytoplasmic cyclin D1 regulates cell invasion and metastasis through the phosphorylation of paxillin
title Cytoplasmic cyclin D1 regulates cell invasion and metastasis through the phosphorylation of paxillin
title_full Cytoplasmic cyclin D1 regulates cell invasion and metastasis through the phosphorylation of paxillin
title_fullStr Cytoplasmic cyclin D1 regulates cell invasion and metastasis through the phosphorylation of paxillin
title_full_unstemmed Cytoplasmic cyclin D1 regulates cell invasion and metastasis through the phosphorylation of paxillin
title_short Cytoplasmic cyclin D1 regulates cell invasion and metastasis through the phosphorylation of paxillin
title_sort cytoplasmic cyclin d1 regulates cell invasion and metastasis through the phosphorylation of paxillin
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4873647/
https://www.ncbi.nlm.nih.gov/pubmed/27181366
http://dx.doi.org/10.1038/ncomms11581
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