This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Li, Z. Articles by Pestell, R. G. Search for Related Content PubMed PubMed Citation Articles by Li, Z. Articles by Pestell, R. G.

Cyclin D1 Regulates Cellular Migration through the Inhibition of Thrombospondin 1 and ROCK Signaling

Department of Cancer Biology, Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania 19107,¹ Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University, 3970 Reservoir Road, NW, Box 571468, Washington, D.C. 20057-1468,² Department of Developmental and Molecular Biology, Albert Einstein College of Medicine, Yeshiva University, Bronx, New York 10461³

Received 2 November 2005/ Returned for modification 13 December 2005/ Accepted 13 March 2006

Cyclin D1 is overexpressed in human tumors, correlating with cellular metastasis, and is induced by activating Rho GTPases. Herein, cyclin D1-deficient mouse embryo fibroblasts (MEFs) exhibited increased adhesion and decreased motility compared with wild-type MEFs. Retroviral transduction of cyclin D1 reversed these phenotypes. Mutational analysis of cyclin D1 demonstrated that its effects on cellular adhesion and migration were independent of the pRb and p160 coactivator binding domains. Genomewide expression arrays identified a subset of genes regulated by cyclin D1, including Rho-activated kinase II (ROCKII) and thrombospondin 1 (TSP-1). cyclin D1^–/– cells showed increased Rho GTP and ROCKII activity and signaling, with increased phosphorylation of LIM kinase, cofilin (Ser3), and myosin light chain 2 (Thr18/Ser19). Cyclin D1 repressed ROCKII and TSP-1 expression, and the migratory defect of cyclin D1^–/– cells was reversed by ROCK inhibition or TSP-1 immunoneutralizing antibodies. cyclin E knockin to the cyclin D1^–/– MEFs rescued the DNA synthesis defect of cyclin D1^–/– MEFs but did not rescue either the migration defect or the abundance of ROCKII. Cyclin D1 promotes cellular motility through inhibiting ROCK signaling and repressing the metastasis suppressor TSP-1.

This article has been cited by other articles:

• Marampon, F., Casimiro, M. C., Fu, M., Powell, M. J., Popov, V. M., Lindsay, J., Zani, B. M., Ciccarelli, C., Watanabe, G., Lee, R. J., Pestell, R. G. (2008). Nerve Growth Factor Regulation of Cyclin D1 in PC12 Cells through a p21RAS Extracellular Signal-regulated Kinase Pathway Requires Cooperative Interactions between Sp1 and Nuclear Factor-{kappa}B. Mol. Biol. Cell 19: 2566-2578 [Abstract] [Full Text]  
• Murooka, T. T., Rahbar, R., Platanias, L. C., Fish, E. N. (2008). CCL5-mediated T-cell chemotaxis involves the initiation of mRNA translation through mTOR/4E-BP1. Blood 111: 4892-4901 [Abstract] [Full Text]  
• Wu, K., Katiyar, S., Li, A., Liu, M., Ju, X., Popov, V. M., Jiao, X., Lisanti, M. P., Casola, A., Pestell, R. G. (2008). Dachshund inhibits oncogene-induced breast cancer cellular migration and invasion through suppression of interleukin-8. Proc. Natl. Acad. Sci. USA 105: 6924-6929 [Abstract] [Full Text]  
• Jiao, X., Katiyar, S., Liu, M., Mueller, S. C., Lisanti, M. P., Li, A., Pestell, T. G., Wu, K., Ju, X., Li, Z., Wagner, E. F., Takeya, T., Wang, C., Pestell, R. G. (2008). Disruption of c-Jun Reduces Cellular Migration and Invasion through Inhibition of c-Src and Hyperactivation of ROCK II Kinase. Mol. Biol. Cell 19: 1378-1390 [Abstract] [Full Text]  
• Li, Z., Wang, C., Jiao, X., Katiyar, S., Casimiro, M. C., Prendergast, G. C., Powell, M. J., Pestell, R. G. (2008). Alternate Cyclin D1 mRNA Splicing Modulates p27KIP1 Binding and Cell Migration. J. Biol. Chem. 283: 7007-7015 [Abstract] [Full Text]  
• Guan, Z., Wang, X.-r., Zhu, X.-f., Huang, X.-f., Xu, J., Wang, L.-h., Wan, X.-b., Long, Z.-j., Liu, J.-n., Feng, G.-k., Huang, W., Zeng, Y.-x., Chen, F.-j., Liu, Q. (2007). Aurora-A, a Negative Prognostic Marker, Increases Migration and Decreases Radiosensitivity in Cancer Cells. Cancer Res. 67: 10436-10444 [Abstract] [Full Text]  
• Kundumani-Sridharan, V., Wang, D., Karpurapu, M., Liu, Z., Zhang, C., Dronadula, N., Rao, G. N. (2007). Suppression of Activation of Signal Transducer and Activator of Transcription-5B Signaling in the Vessel Wall Reduces Balloon Injury-Induced Neointima Formation. Am. J. Pathol. 171: 1381-1394 [Abstract] [Full Text]  
• Ostrander, J. H., Daniel, A. R., Lofgren, K., Kleer, C. G., Lange, C. A. (2007). Breast Tumor Kinase (Protein Tyrosine Kinase 6) Regulates Heregulin-Induced Activation of ERK5 and p38 MAP Kinases in Breast Cancer Cells. Cancer Res. 67: 4199-4209 [Abstract] [Full Text]  
• Ju, X., Katiyar, S., Wang, C., Liu, M., Jiao, X., Li, S., Zhou, J., Turner, J., Lisanti, M. P., Russell, R. G., Mueller, S. C., Ojeifo, J., Chen, W. S., Hay, N., Pestell, R. G. (2007). Akt1 governs breast cancer progression in vivo. Proc. Natl. Acad. Sci. USA 104: 7438-7443 [Abstract] [Full Text]  
• Wang, D., Liu, Z., Li, Q., Karpurapu, M., Kundumani-Sridharan, V., Cao, H., Dronadula, N., Rizvi, F., Bajpai, A. K., Zhang, C., Muller-Newen, G., Harris, K. W., Rao, G. N. (2007). An Essential Role for gp130 in Neointima Formation Following Arterial Injury. Circ. Res. 100: 807-816 [Abstract] [Full Text]  
• Katiyar, S., Jiao, X., Wagner, E., Lisanti, M. P., Pestell, R. G. (2007). Somatic Excision Demonstrates that c-Jun Induces Cellular Migration and Invasion through Induction of Stem Cell Factor. Mol. Cell. Biol. 27: 1356-1369 [Abstract] [Full Text]  
• Fu, M., Liu, M., Sauve, A. A., Jiao, X., Zhang, X., Wu, X., Powell, M. J., Yang, T., Gu, W., Avantaggiati, M. L., Pattabiraman, N., Pestell, T. G., Wang, F., Quong, A. A., Wang, C., Pestell, R. G. (2006). Hormonal Control of Androgen Receptor Function through SIRT1. Mol. Cell. Biol. 26: 8122-8135 [Abstract] [Full Text]  
• Li, Z., Jiao, X., Wang, C., Ju, X., Lu, Y., Yuan, L., Lisanti, M. P., Katiyar, S., Pestell, R. G. (2006). Cyclin D1 Induction of Cellular Migration Requires p27KIP1.. Cancer Res. 66: 9986-9994 [Abstract] [Full Text]