Cytoplasmic cyclin D1 regulates cell invasion and metastasis through the phosphorylation of paxillin
Pérez Fusté, Noel
Fernández Hernández, Rita
Mirantes Barbeito, Cristina
Dolcet Roca, Xavier
MetadataShow full item record
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.
Is part ofNature Communications, 2016, vol. 7, núm. 11581
European research projects
The following license files are associated with this item:
Showing items related by title, author, creator and subject.
Pérez Fusté, Noel; Castelblanco Echavarría, Esmeralda; Felip, Isidre; Santacana Espasa, Maria; Fernández-Hernández, Rita; Gatius Calderó, Sònia; Pedraza González, Neus; Pallares, Judit; Cemeli, Tània; Valls Marsal, Joan; Tarres, Marc; Ferrezuelo, Francisco; Dolcet Roca, Xavier; Matias-Guiu, Xavier; Garí Marsol, Eloi (Impact Journals, 2016)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 ...
Cemeli, Tània; Guasch Vallés, Marta; Nàger Grifo, Mireia; Felip, Isidre; Cambray Carner, Serafí; Santacana Espasa, Maria; Gatius Calderó, Sònia; Pedraza González, Neus; Dolcet Roca, Xavier; Ferrezuelo, Francisco; Schuhmacher, Alberto J.; Herreros Danés, Judit; Garí Marsol, Eloi (Wiley, 2019)Glioblastoma (GBM) is a highly invasive brain neoplasia with an elevated recurrence rate after surgical resection. The CyclinD1 (Ccnd1)/Cdk4-RB1 axis is frequently altered in GBM, leading to over-proliferation by RB1 ...
Cyclin D1 localizes in the cytoplasm of keratinocytes during skin differentiation and regulates cell–matrix adhesion Fernández Hernández, Rita; Rafel i Borrell, Marta; Pérez Fusté, Noel; Aguayo Ortiz, Rafael; Casanova i Seuma, Josep M. (Josep Manel); Egea Navarro, Joaquim; Ferrezuelo, Francisco; Garí Marsol, Eloi (Taylor & Francis, 2013)The function of Cyclin D1 (CycD1) has been widely studied in the cell nucleus as a regulatory subunit of the cyclindependent kinases Cdk4/6 involved in the control of proliferation and development in mammals. CycD1 has ...