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

Protein phosphatases limit tumor motility

M R Young1, Y Lozano, A Djorjevic

  • 1Department of Research Services, Hines V.A. Hospital, IL 60141.

International Journal of Cancer
|July 30, 1993
PubMed
Summary

Non-metastatic cancer cells show increased motility when protein phosphatases (PP-1/2A) are inhibited, suggesting their activity restricts PKA-stimulated cell movement. This restriction is deficient in metastatic cells, leading to enhanced migration and invasion.

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

First Constraints on the Epoch of Reionization Using the Non-Gaussianity of the Kinematic Sunyaev-Zel'dovich Effect from the South Pole Telescope and Herschel-SPIRE Observations.

Physical review letters·2024
Same author

Broadband, millimeter-wave antireflection coatings for large-format, cryogenic aluminum oxide optics.

Applied optics·2020
Same author

Supersymmetric AdS6 via T duality.

Physical review letters·2014
Same author

The incidence of Trichinella spiralis at necropsies in England.

Journal of helminthology·2010
Same author

Statistical properties of a laser with multiplicative noise.

Optics letters·2009
Same author

Aerosol-delivered programmed cell death 4 enhanced apoptosis, controlled cell cycle and suppressed AP-1 activity in the lungs of AP-1 luciferase reporter mice.

Gene therapy·2007

Area of Science:

  • Cancer Biology
  • Cell Motility
  • Signal Transduction

Background:

  • Prostaglandin E2 (PGE2) elevates cyclic AMP (cAMP), activating protein kinase A (PKA) and stimulating metastasis in Lewis lung carcinoma cells (LLC-LN7).
  • Non-metastatic LLC (LLC-C8) cells are unresponsive to cAMP elevation despite normal PKA enzyme levels.
  • This unresponsiveness may stem from increased dephosphorylation by serine/threonine protein phosphatases (PP-1/2A).

Purpose of the Study:

  • To investigate the role of PP-1/2A in PKA-unresponsiveness and motility of non-metastatic LLC-C8 cells.
  • To compare phosphatase activity and its effect on motility between metastatic (LLC-LN7) and non-metastatic (LLC-C8) Lewis lung carcinoma cells.

Main Methods:

  • Treatment of LLC-C8 cells with okadaic acid, a PP-1/2A inhibitor, to assess effects on migration and invasion.

Related Experiment Videos

  • Inhibition of PKA activity to determine its role in okadaic acid-stimulated motility.
  • Dose-response studies using okadaic acid and calyculin A to selectively inhibit PP-2A and PP-1.
  • Enzyme activity assays to compare PP-1/2A levels in LLC variants.

    • Main Results:

    • Okadaic acid significantly increased LLC-C8 cell motility, comparable to LLC-LN7 cells.
    • PGE2 further enhanced motility in okadaic acid-treated LLC-C8 cells, indicating PKA pathway involvement.
    • Inhibition of PP-1 and PP-2A progressively increased LLC-C8 cell migration, suggesting both phosphatases limit motility.
    • Non-metastatic LLC-C8 cells exhibited higher PP-1/2A activity than metastatic LLC-LN7 cells.
    • LLC-C8 cells showed activity of both PP-1 and PP-2A, while LLC-LN7 cells had PP-1 and reduced PP-2A activity.

    Conclusions:

    • PKA-stimulated cell motility is actively restricted by both PP-1 and PP-2A in non-metastatic Lewis lung carcinoma cells.
    • A deficiency in this phosphatase-mediated restriction contributes to the increased migration and invasion observed in metastatic cancer cells.
    • Targeting these phosphatases could offer a strategy to modulate cancer cell metastasis.