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Mitotic Centromere-Associated Kinesin (MCAK/KIF2C) Regulates Cell Migration and Invasion by Modulating Microtubule

Ha Hyung Moon1, Nina-Naomi Kreis1, Alexandra Friemel1

  • 1Obstetrics and Prenatal Medicine, Department of Gynecology and Obstetrics, University Hospital Frankfurt, J. W. Goethe-University Frankfurt, Theodor-Stern-Kai 7, D-60590 Frankfurt, Germany.

Cancers
|November 27, 2021
PubMed

Insights

Mitotic centromere-associated kinesin (MCAK) regulates cell motility and migration. Both increased and decreased MCAK levels impair cell movement and focal adhesion dynamics, impacting tumor metastasis.

Area of Science:

  • Cell Biology
  • Cytoskeleton Dynamics
  • Cancer Research

Background:

  • Microtubule (MT) dynamics are crucial for cell motility and migration.
  • Mitotic centromere-associated kinesin (MCAK/KIF2C) regulates MT dynamics and is implicated in cancer metastasis.
  • The precise molecular mechanisms of MCAK's role in cell migration are not fully understood.

Purpose of the Study:

  • To investigate the role of MCAK in cell motility and migration.
  • To elucidate the molecular mechanisms by which MCAK affects cell movement and focal adhesion turnover.
  • To determine the impact of MCAK dysregulation on malignant progression.

Main Methods:

  • Generated CRISPR/dCas9 HeLa and retinal pigment epithelium (RPE) cell lines with MCAK overexpression or downregulation.
  • Assessed cell motility and migration.
  • Analyzed focal adhesion (FA) protein composition, phosphorylation status, and turnover rates.
  • Examined spindle and chromosome segregation.
  • Investigated microtubule plus-tip dynamics.

Main Results:

  • Both upregulation and downregulation of MCAK reduced cell motility and migration in benign and malignant cells.
  • MCAK dysregulation impaired FA protein composition and phosphorylation, and disturbed FA assembly/disassembly rates.
  • Spindle and chromosome segregation were affected, cell adhesion was delayed, and MT plus-tip dynamics were compromised.
  • MCAK influences actin-MT cytoskeleton dynamics and FA turnover.

Conclusions:

  • MCAK is a critical regulator of cell motility and migration.
  • Dysregulated MCAK impacts cytoskeleton dynamics and focal adhesion turnover, potentially promoting tumor progression and metastasis.
  • Understanding MCAK's mechanisms provides insights into cancer metastasis.
Keywords:
CRISPR/dCas9MCAKactin cytoskeletondepolymerizationfocal adhesioninvasionmicrotubule dynamicsmigrationmotilityplus-tip

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