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FMN2 Makes Perinuclear Actin to Protect Nuclei during Confined Migration and Promote Metastasis

Colleen T Skau1, Robert S Fischer1, Pinar Gurel1

  • 1Cell Biology and Physiology Center, National Heart Lung and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA.

Cell
|November 15, 2016
PubMed

Insights

A newly discovered perinuclear actin system, driven by FMN2, protects cell nuclei during migration in confined spaces. This mechanism is crucial for cancer cell survival and metastasis.

Area of Science:

  • Cell Biology
  • Biophysics
  • Cancer Research

Background:

  • Cell migration in confined 3D environments is vital for physiological processes and tumor spread.
  • Nuclear integrity is challenged during migration, potentially leading to DNA damage.
  • Actin cytoskeleton dynamics play a key role in cell mechanics and migration.

Purpose of the Study:

  • To identify cytoskeletal mechanisms protecting the nucleus during migration in confined 3D microenvironments.
  • To investigate the role of the formin-family protein FMN2 in nuclear protection and cell survival.
  • To determine the involvement of FMN2 in melanoma cell metastasis.

Main Methods:

  • Utilized live-cell imaging and microscopy to observe cytoskeletal structures and nuclear dynamics.
  • Investigated the function of FMN2 using genetic manipulation (disruption) in cell and animal models.
  • Analyzed FMN2 expression levels in human melanoma samples.

Main Results:

  • Discovered a novel perinuclear actin/focal adhesion (FA) system regulated by FMN2.
  • This FMN2-dependent system controls nuclear shape and positioning.
  • FMN2 protects the nucleus from damage and DNA double-strand breaks in confined 3D migration.
  • FMN2 is upregulated in human melanomas; its disruption inhibits melanoma cell extravasation and lung metastasis in mice.

Conclusions:

  • FMN2 is essential for generating a protective perinuclear actin/FA system during confined cell migration.
  • This system safeguards nuclear and DNA integrity, promoting cell survival.
  • FMN2 plays a significant role in promoting cancer cell metastasis, highlighting its potential as a therapeutic target.
Keywords:
DNA damageactincell migrationconfined migrationfocal adhesionforminmelanomametastasisstress fiberventral actin bundle

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