Cell cycle-dependent force transmission in cancer cells

Area of Science:

• Cell Biology
• Biophysics
• Cancer Research

Background:

• Cell migration is essential for tumor dissemination.
• Nuclear stiffness changes cyclically during the cell cycle in cancer cells.
• The mechanical forces cells exert are critical for invasion but the cell cycle regulation is unclear.

Purpose of the Study:

• To investigate the relationship between cell cycle progression and the forces cancer cells generate.
• To explore the role of paxillin phosphorylation in regulating these forces.
• To understand the mechanical framework of cancer cell invasion.

Main Methods:

• Human epithelial cancer cells were engineered with the Fucci2 reporter to track cell cycle phases.
• Reference-free confocal traction-force microscopy was used to measure cell-generated forces.
• Paxillin phosphorylation levels were analyzed and manipulated using FAK inhibition and mutant paxillin transfection.

Main Results:

• Cell-generated forces were significantly higher during the G1 and early S phases compared to late S/G2 phases.
• These forces colocalized with increased paxillin phosphorylation at focal adhesions.
• Inhibiting FAK or altering paxillin phosphorylation reduced the forces transmitted to the substrate.

Conclusions:

• Cancer cell force transmission is reproducibly modulated during the cell cycle.
• Paxillin phosphorylation is a key regulator of adhesion maturation and force transmission.
• This mechanism is instrumental for cancer cell invasion into dense environments.