Related Experiment Video
Updated: Aug 8, 2026

Optogenetic Inhibition of Rho1-Mediated Actomyosin Contractility Coupled with Measurement of Epithelial Tension in Drosophila Embryos
Published on: April 14, 2023
Cyclin D1 regulates cellular migration through the inhibition of thrombospondin 1 and ROCK signaling
Zhiping Li1, Chenguang Wang, Xuanmao Jiao
1Thomas Jefferson University, Department of Cancer Biology, Kimmel Cancer Center, Bluemle Building, Rm 1050, 233 South 10th St, Philadelphia, PA 19107, USA.
Abstract:
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.
Insights
Cyclin D1, overexpressed in tumors, promotes cell motility by inhibiting Rho-activated kinase II (ROCKII) signaling and repressing metastasis suppressor thrombospondin 1 (TSP-1). Loss of cyclin D1 increases adhesion and decreases motility.
Area of Science:
- Oncology
- Cell Biology
- Molecular Biology
Background:
- Cyclin D1 is frequently overexpressed in human tumors and linked to metastasis.
- Activation of Rho GTPases induces cyclin D1 expression.
- The precise role of cyclin D1 in regulating cell adhesion and motility remains incompletely understood.
Purpose of the Study:
- To investigate the role of cyclin D1 in regulating cellular adhesion, motility, and associated molecular pathways.
- To identify genes regulated by cyclin D1 that influence cell migration.
- To elucidate the mechanism by which cyclin D1 affects cell metastasis.
Main Methods:
- Utilized cyclin D1-deficient mouse embryo fibroblasts (MEFs) and wild-type MEFs for comparative analysis.
- Employed retroviral transduction to reintroduce cyclin D1 into deficient cells.
- Performed mutational analysis of cyclin D1, genomewide expression arrays, and Rho GTPase activity assays.
Main Results:
- Cyclin D1 deficiency led to increased cell adhesion and decreased motility, which were reversed by cyclin D1 reintroduction.
- Cyclin D1 regulates genes including Rho-activated kinase II (ROCKII) and thrombospondin 1 (TSP-1).
- Cyclin D1-deficient cells exhibited elevated Rho GTP, ROCKII activity, and downstream signaling, alongside repressed ROCKII and TSP-1 expression.
Conclusions:
- Cyclin D1 promotes cellular motility by inhibiting ROCK signaling pathways.
- Cyclin D1 acts as a repressor of the metastasis suppressor TSP-1.
- Targeting cyclin D1 or its downstream effectors may offer therapeutic strategies for inhibiting cancer metastasis.
Related Concept Videos
Inhibition of Cdk Activity
Inhibition of CDK Activity
Cytoskeletal Coordination in Cell Migration
Cell Migration
Cell Migration
Positive Regulator Molecules

