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Title:
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Cytoplasmic cyclin D1 regulates cell invasion and metastasis through the phosphorylation of paxillin
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Author:
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Pérez Fusté, Noel; Fernández Hernández, Rita; Cemeli, Tània; Mirantes Barbeito, Cristina; Pedraza González, Neus; Rafel i Borrell, Marta; Torres Rosell, Jordi; Colomina i Gabarrella, Neus; Ferrezuelo, Francisco; Dolcet Roca, Xavier; Garí Marsol, Eloi
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Notes:
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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.
This work was funded by Spanish Ministry of Education and Science (BFU2013-42895) (CSD2007-00015), grants BFU2015–71308 and BFU2013–50245-EXP from the Spanish Ministry of Economy and Competitivity, Catalan Government (SGR-559), and Fondo de Investigaciones Sanitarias (PI10/00604). |
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Rights:
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cc-by (c) Fusté et al., 2016
http://creativecommons.org/licenses/by/3.0/es/
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Document type:
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publishedVersion |
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Published by:
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Nature Publishing Group
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