Switching in discoid domain receptor expressions in SLUG-induced epithelial-mesenchymal transition

Area of Science:

• Cell Biology
• Molecular Biology
• Cancer Research

Background:

• Epithelial-mesenchymal transition (EMT) is a process where cells lose epithelial characteristics and gain migratory and invasive properties.
• The specific cellular changes and responses to extracellular matrices (ECMs) during EMT are not fully understood.

Purpose of the Study:

• To investigate alterations in proliferative potential and ECM responsiveness in cells undergoing EMT.
• To identify molecular changes associated with EMT, focusing on cell cycle regulation and receptor tyrosine kinases.

Main Methods:

• Utilized MDCK cells and SLUG-transfected MDCK clones (SLUG-MDCK) to model EMT.
• Analyzed cell cycle progression using flow cytometry and Western blotting.
• Assessed ECM-stimulated proliferation with collagen, fibronectin, and laminin, and detected protein phosphorylation via immunoprecipitation-Western assays.

Main Results:

• SLUG-MDCK cells exhibited G1 and G2/M cell cycle arrest, mediated partly by p21WAF1/Cip1 and Wee1.
• Exposure to type I collagen induced significant proliferation (6-fold increase) in SLUG-MDCK cells, linked to Wee1 degradation.
• A notable increase in discoidin domain receptor (DDR) 2 expression and a decrease in DDR1 were observed in SLUG-MDCK cells, with functional DDR2 phosphorylation on collagen.

Conclusions:

• SLUG-induced EMT alters the expression of receptor tyrosine kinases, specifically discoidin domain receptors (DDRs).
• The shift in DDR expression (DDR1 to DDR2) may contribute to altered cellular behavior and proliferation in EMT.
• Similar DDR expression changes were observed in naturally dedifferentiated human liver cancer cell lines, suggesting relevance in cancer progression.