The Scribble-Rac1 signaling axis drives epithelial cell motility and contributes to diffuse adenomyosis pathogenesis.

PURPOSE: The study was designed to investigate whether estrogen regulates cell migration through cell polarity signaling and contributes to adenomyosis development.

METHODS

In vitro study, Ishikawa cells received different treatments, Western Blot was used to detect the expression of adhesion factors and cytoskeletal proteins. Pseudopodia formation was assessed by cell immunofluorescence staining. Scratch test and transwell invasion test were used to detect the changes in Ishikawa cell migration and invasion.

RESULTS

Scribble expression in Ishikawa cells is down-regulated by estrogen, leading to reduced expression of adhesion factors, increased expression of cytoskeletal proteins, enhanced pseudopodia formation, and elevated cell motility and invasion. Molecular mechanism research suggests that reduced Scribble expression may promote cell motility and invasion through activation of the Rac1-IRSp53-WAVE2 signaling pathway.

CONCLUSIONS

Scribble downregulation may serve as an indicator of adenomyosis severity. Its reduction alters cytoskeletal protein expression, enhancing cell motility. Mechanistically, Scribble downregulation likely activates Rac1, triggering the Rac1/IRSp53/WAVE2 pathway, which promotes pseudopodia formation and increases cell migration. These insights provide a theoretical basis for understanding the pathogenesis of adenomyosis.