Jove
Visualize
Contact Us
JoVE
x logofacebook logolinkedin logoyoutube logo
ABOUT JoVE
OverviewLeadershipBlogJoVE Help Center
AUTHORS
Publishing ProcessEditorial BoardScope & PoliciesPeer ReviewFAQSubmit
LIBRARIANS
TestimonialsSubscriptionsAccessResourcesLibrary Advisory BoardFAQ
RESEARCH
JoVE JournalMethods CollectionsJoVE Encyclopedia of ExperimentsArchive
EDUCATION
JoVE CoreJoVE BusinessJoVE Science EducationJoVE Lab ManualFaculty Resource CenterFaculty Site
Terms & Conditions of Use
Privacy Policy
Policies

Related Experiment Videos

Alpha(v)beta3 integrin expression up-regulates cdc2, which modulates cell migration.

Thomas Manes1, Duo-Qi Zheng, Simona Tognin

  • 1Department of Pathology, Yale University School of Medicine, New Haven, CT 06510, USA.

The Journal of Cell Biology
|May 29, 2003
PubMed
Summary

The integrin alphavbeta3 activates a new cell migration pathway. This pathway involves cdc2 (cell division cycle 2), which promotes cancer cell motility by interacting with cyclin B2 and caldesmon.

Related Concept Videos

You might also read

Related Articles

Articles linked to this work by shared authors, journal, and citation graph.

Sort by
Same author

Advancements in extracellular vesicle research.

Extracellular vesicle·2026
Same author

A novel sialylation pathway mediated by extracellular vesicles in aggressive prostate cancer.

PloS one·2025
Same author

Parkin Induces Ubiquitination and Large Extracellular Vesicle Release of HMGB1 to Activate Antitumor Immunity.

Cancer research·2025
Same author

Irradiation of prostate cancer alters circulating small extracellular vesicle functions.

Scientific reports·2025
Same author

Exploring STEAP1 Expression in Prostate Cancer Cells in Response to Androgen Deprivation and in Small Extracellular Vesicles.

Molecular cancer research : MCR·2025
Same author

Role of Kindlin 2 in prostate cancer.

Scientific reports·2024

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Cancer Research

Background:

  • Integrins, such as alphavbeta3, are cell surface receptors that play critical roles in cell adhesion and migration.
  • Previous studies indicate alphavbeta3 integrin promotes cell migration via intracellular signaling pathways.

Purpose of the Study:

  • To elucidate a novel pathway regulating cell migration.
  • To investigate the role of cdc2 (cdk1) as a downstream effector of alphavbeta3 integrin in modulating cell motility.

Main Methods:

  • Gene expression analysis to quantify cdc2 mRNA levels.
  • Western blotting and kinase assays to assess cdc2 protein and activity.
  • Cell migration assays with ectopic expression, dominant-negative constructs, and pharmacological inhibitors.

Related Experiment Videos

  • Co-immunoprecipitation to study protein-protein interactions (cdc2 and cyclin B2).
  • Immunofluorescence microscopy to determine subcellular localization of cdc2 and caldesmon.

    • Main Results:

    • alphavbeta3 integrin expression in prostate cancer cells (beta3-LNCaP) significantly increased cdc2 mRNA, protein levels, and kinase activity.
    • Increased cdc2 levels correlated with enhanced cancer cell motility.
    • Ectopic cdc2 expression promoted cell migration, while dominant-negative cdc2 inhibited it.
    • cdc2 inhibitors reduced cell migration without impacting cell adhesion.
    • cdc2 associates with cyclin B2 to promote cell migration.
    • A novel pathway involving cdc2 and caldesmon was identified, with both proteins localizing to membrane ruffles in motile cells.

    Conclusions:

    • cdc2 is a novel downstream effector of alphavbeta3 integrin signaling.
    • The alphavbeta3-cdc2-cyclin B2-caldesmon pathway is critical for promoting cell migration.
    • Targeting this pathway could offer therapeutic strategies for cancers with altered integrin expression.