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Updated: Jan 13, 2026

A Simplified and Efficient Method to Isolate Primary Human Keratinocytes from Adult Skin Tissue
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Inactivation of Focal Adhesion Kinase FAK Rapidly Abrogates Keratinocyte Entry in Mitosis via Rho-Associated Kinase,

Lizbeth Contreras1, Lorena García-Gaipo1, Fe García-Reija1,2

  • 1Cell Cycle, Stem Cell Fate and Cancer Laboratory, Institute for Research of Marqués de Valdecilla (IDIVAL), Santander, Spain.

FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology
|January 12, 2026
PubMed

Insights

Focal adhesion kinase (FAK) inactivation rapidly halts cell division and triggers differentiation in epithelial cells. This Rock-dependent switch acts as a checkpoint, preventing proliferation and promoting homeostasis in stratified epithelia.

Area of Science:

  • Cell biology
  • Epithelial biology
  • Cancer research

Background:

  • Cell adhesion is crucial for epithelial homeostasis and proliferation control.
  • Focal adhesion kinase (FAK) is implicated in cell adhesion signaling, cancer, and proliferation.
  • The precise mechanisms of FAK in regulating the epithelial cell cycle remain incompletely understood.

Purpose of the Study:

  • To investigate the role of FAK in the keratinocyte cell cycle.
  • To determine if FAK influences the previously identified mitosis-differentiation checkpoint.
  • To elucidate the downstream pathways involved in FAK-mediated cell cycle control.

Main Methods:

  • Inactivation of FAK in normal human oral keratinocytes using shRNAs and the inhibitor defactinib.
  • Synchronization of human epidermal N-TERT cells in prometaphase.
  • Assessment of cell cycle progression, mitotic entry, and differentiation markers.
  • Inhibition of Rho-associated kinase (Rock) to assess its role in FAK-mediated effects.

Main Results:

  • FAK inactivation rapidly blocked entry into mitosis and induced a differentiation response, independent of DNA damage.
  • Tumor suppressor P53 was induced, while Cyclin B nuclear translocation was inhibited.
  • Synchronized cells failed to complete mitosis upon FAK inhibition.
  • Concomitant inhibition of Rock rescued mitotic progression, indicating a Rock-dependent mechanism.

Conclusions:

  • FAK inactivation triggers a rapid, Rock-dependent switch that halts mitosis and induces terminal differentiation in epithelial cells.
  • This mechanism acts as a checkpoint to suppress suprabasal proliferation of precancerous cells.
  • FAK plays a critical role in regulating the mitosis-differentiation balance in stratified epithelia.
Keywords:
cell adhesioncell fatedifferentiationepitheliahomeostasismitosissquamous carcinoma

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