Epithelial-to-Mesenchymal Plasticity Harnesses Endocytic Circuitries

Area of Science:

• Cell Biology
• Molecular Biology
• Cancer Research

Background:

• Cellular plasticity, including epithelial-to-mesenchymal transition (EMT), is crucial for development, tissue repair, and disease pathogenesis like cancer and fibrosis.
• EMT involves significant genetic, epigenetic, and proteomic changes, leading to altered cell adhesion, polarity, and motility.
• Loss of cell polarity is a hallmark of EMT, preceding other changes and transforming epithelial cells into motile mesenchymal cells.

Purpose of the Study:

• To explore the role of endocytosis in regulating cellular plasticity and the epithelial-to-mesenchymal transition (EMT).
• To understand how endocytic pathways influence dynamic changes in cell identity and adaptation during EMT.
• To highlight the impact of EMT-driven endocytosis on physiological and pathological processes, especially cancer progression.

Main Methods:

• Time-resolved proteomic and phosphoproteomic analyses of cells undergoing EMT.
• Investigation of genetic and epigenetic alterations during the transition.
• Analysis of protein expression and post-translational modifications.

Main Results:

• EMT is a gradual, dynamic, and often reversible process, generating heterogeneous cell populations.
• Thousands of protein changes were identified, including unexpected alterations in membrane trafficking.
• Endocytic circuitries are implicated in controlling EMT and its associated cellular changes.

Conclusions:

• Endocytosis is a critical regulator of EMT, influencing cell identity, flexibility, and adaptation.
• EMT-driven endocytosis contributes to cellular heterogeneity in both normal tissues and disease states.
• Understanding the interplay between endocytosis and EMT is vital for addressing cancer progression and other pathologies.