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

Dormant disseminated tumor cells (DTC) can survive long-term and drive metastatic relapse years to decades after primary tumor treatment, which remains a major clinical problem. Epithelial-to-mesenchymal transition (EMT) allows these dormant cells to evade immune surveillance, highlighting a potential therapeutic target to prevent metastatic recurrence. In a recent study, Wang and colleagues demonstrated that a TGFβ-driven atypical or hybrid EMT state allows lung adenocarcinoma cells to evade the immune system and persist in a dormant state. This atypical EMT state relies on the upregulation of the cytoskeletal protein gelsolin, which mediates the conversion to round, softer cells that are resistant to immune surveillance and promote dormant cell survival. The inhibition of TGFβ or gelsolin prevents the change in cell morphology, and the cells remain stiff and become susceptible to immune clearance in vivo. This study identifies a novel vulnerability of dormant tumor cells that could be exploited to eliminate dormant DTCs and prevent metastatic relapse.