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Cytoplasmic cyclin D1 regulates cell invasion and metastasis through the phosphorylation of paxillin.
- Source :
-
Nature communications [Nat Commun] 2016 May 16; Vol. 7, pp. 11581. Date of Electronic Publication: 2016 May 16. - Publication Year :
- 2016
-
Abstract
- 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.
- Subjects :
- Animals
Cell Line, Tumor
Cell Membrane metabolism
Cyclin D1 deficiency
Cyclin-Dependent Kinase 4 metabolism
Down-Regulation genetics
Fibroblasts metabolism
Gene Knockdown Techniques
HEK293 Cells
Humans
Mice
Neoplasm Invasiveness
Neoplasm Metastasis
Phosphorylation
Phosphoserine metabolism
Protein Binding
Rats
Substrate Specificity
rac1 GTP-Binding Protein metabolism
Cyclin D1 metabolism
Cytoplasm metabolism
Neoplasms metabolism
Neoplasms pathology
Paxillin metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 2041-1723
- Volume :
- 7
- Database :
- MEDLINE
- Journal :
- Nature communications
- Publication Type :
- Academic Journal
- Accession number :
- 27181366
- Full Text :
- https://doi.org/10.1038/ncomms11581