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Involvement of SASH1 in the Maintenance of Stable Cell-Cell Adhesion
A S Ilnitskaya1, I Y Zhitnyak1, N A Gloushankova2
1Blokhin National Medical Research Center of Oncology, Ministry of Health of the Russian Federation, Moscow, 115478, Russia.
Biochemistry. Biokhimiia
|June 27, 2020
Summary
The SASH1 protein is crucial for maintaining stable cell-cell adhesion in epithelial cells. Its depletion disrupts adherens junctions, leading to a mesenchymal phenotype, suggesting a role in preventing tumor progression.
Area of Science:
- Cell Biology
- Molecular Biology
- Cancer Research
Background:
- SASH1 is an adapter and signaling protein involved in protein-protein interactions.
- Downregulation of SASH1 is frequently observed in various types of tumors.
Purpose of the Study:
- To investigate the localization and function of SASH1 in normal and cancer cells during epithelial-mesenchymal transition (EMT).
- To determine the role of SASH1 in maintaining cell-cell adhesion.
Main Methods:
- Immunofluorescence staining and confocal microscopy were used to examine SASH1 localization in IAR-20 (normal epithelial) and HT-29 (colorectal cancer) cells.
- Epithelial-mesenchymal transition (EMT) was induced using Epidermal Growth Factor (EGF).
- RNA interference was employed to deplete SASH1 in IAR-20 cells.
Main Results:
- SASH1 co-localized with adherens junctions (AJs) and circumferential actin bundles in both normal and epithelial cancer cells.
- During EMT, SASH1 remained in unstable AJs in partially transitioned cells but was lost from cell-cell contacts in completely transitioned cells.
- SASH1 depletion in IAR-20 cells led to the disruption of stable AJs and induced a mesenchymal phenotype.
Conclusions:
- SASH1 plays a significant role in the maintenance of stable cell-cell adhesion.
- The findings suggest SASH1's involvement in regulating the epithelial-mesenchymal transition process.
- SASH1 may function as a tumor suppressor by preserving epithelial integrity.
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