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
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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.
Is part ofNature Communications, 2016, vol. 7, núm. 11581
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