Acting on Dormancy: The Interplay Between the Actin Cytoskeleton and Tumor Cell Dormancy

Area of Science:

• Oncology
• Cell Biology
• Immunology

Background:

• Dormant disseminated tumor cells (DTCs) pose a significant clinical challenge, leading to metastatic relapse years after primary treatment.
• Epithelial-mesenchymal transition (EMT) is implicated in immune evasion by dormant DTCs, suggesting it as a therapeutic target.

Purpose of the Study:

• To investigate the role of transforming growth factor-β (TGF-β) and gelsolin in maintaining the dormancy and immune evasion of lung adenocarcinoma cells.
• To identify therapeutic strategies targeting dormant DTCs to prevent metastatic recurrence.

Main Methods:

• The study examined TGF-β-driven atypical EMT in lung adenocarcinoma cells.
• Gelsolin's role in mediating cell morphology changes and immune resistance was assessed.
• The effects of inhibiting TGF-β or gelsolin on cell stiffness and immune clearance were evaluated in vivo.

Main Results:

• A TGF-β-driven atypical EMT state promotes immune evasion and dormancy in lung adenocarcinoma cells.
• Upregulation of gelsolin facilitates conversion to round, softer cells resistant to immune surveillance.
• Inhibition of TGF-β or gelsolin maintained cell stiffness, rendering dormant cells susceptible to immune clearance.

Conclusions:

• This study identifies a novel vulnerability in dormant tumor cells.
• Targeting gelsolin or TGF-β could be a promising strategy to eliminate dormant DTCs and prevent metastatic relapse.