Related Experiment Video
Updated: Jul 28, 2026

In vitro Cell Migration and Invasion Assays
Published on: June 1, 2014
Focal adhesion kinase activates Stat1 in integrin-mediated cell migration and adhesion
1Department of Pathology, Yale University School of Medicine, New Haven, Connecticut 06520-8023, USA.
Abstract:
Recent studies suggest that focal adhesion kinase (FAK) is important for cell migration. We now suggest a mechanism by which FAK activates the signal transducer and activator of transcription (STAT) pathway, regulating cell adhesion and migration. In particular, we observe that FAK is capable of activating Stat1, but not Stat3. Co-immunoprecipitation and in vitro binding assays demonstrate that Stat1 is transiently and directly associated with FAK during cell adhesion, and Stat1 is activated in this process. FAK with a C-terminal deletion (FAKDeltaC14) completely abolishes this interaction, indicating this association is dependent on the C-terminal domain of FAK, which is required for FAK localization at focal contacts. Moreover, Stat1 activation during cell adhesion is diminished in FAK-deficient cells, correlating with decreased migration in these cells. Finally, we show that depletion of Stat1 results in an enhancement of cell adhesion and a decrease in cell migration. Thus, our results have demonstrated, for the first time, a critical signaling pathway from integrin/FAK to Stat1 that reduces cell adhesion and promotes cell migration.
Insights
Focal adhesion kinase (FAK) activates Stat1, a signaling pathway that reduces cell adhesion and promotes cell migration. This discovery reveals a new mechanism regulating cell movement.
Area of Science:
- Cell Biology
- Molecular Biology
- Biochemistry
Background:
- Focal adhesion kinase (FAK) plays a crucial role in cell migration.
- The precise mechanisms by which FAK influences cell adhesion and migration are still being elucidated.
Purpose of the Study:
- To investigate the mechanism by which FAK regulates cell adhesion and migration.
- To determine if FAK activates the signal transducer and activator of transcription (STAT) pathway.
Main Methods:
- Co-immunoprecipitation and in vitro binding assays were used to assess the interaction between FAK and STAT proteins.
- FAK-deficient cells and cells with a C-terminal deletion of FAK (FAKDeltaC14) were utilized.
- Depletion of Stat1 was performed to evaluate its role in cell adhesion and migration.
Main Results:
- FAK directly activates Stat1, but not Stat3, during cell adhesion.
- Stat1 transiently associates with FAK via its C-terminal domain, which is essential for FAK localization at focal contacts.
- Stat1 activation is reduced in FAK-deficient cells, leading to decreased cell migration.
- Depletion of Stat1 enhances cell adhesion and reduces cell migration.
Conclusions:
- A novel signaling pathway involving integrin/FAK activation of Stat1 has been identified.
- This pathway is critical for reducing cell adhesion and promoting cell migration.
- FAK-mediated Stat1 activation represents a key regulatory mechanism in cell motility.
Related Concept Videos
Cell Migration
MAPK Signaling Cascades
The JAK-STAT Signaling Pathway
Integrins
Some ECM proteins assemble into a basement membrane to which the remaining components adhere. Proteoglycans typically form the bulk of the ECM while fibrous proteins, like collagen,...
Activation of Integrins
In "outside-in signaling," external factors in the extracellular space bind to exposed ligand binding sites on integrins. This causes the inactive protein to undergo a conformational change to become active. Integrins are often clustered on the cell membrane. Repetitive and regularly spaced ligand binding events provide an effective stimulus.
Intracellular Signaling Affects Focal Adhesions
Some...

