Dynamic regulation of cAMP levels in entosis: implications for cancer development

Abstract

Entosis is a non-apoptotic cell death process characterized by the formation of cell-in-cell structures in cancer cells. Cyclic AMP (cAMP) is a crucial signaling molecule regulating various cellular processes, including cell death, stress responses, cell-cell interactions, and cancer development. Although cAMP shares several mechanisms with entosis, its specific role in this process remains unclear. In this study, we aimed to elucidate the involvement and dynamics of cAMP during entosis. Elevation of cAMP levels via forskolin reduced entosis efficiency. Monitoring with a membrane-localized cAMP indicator revealed spatiotemporal variations in local cAMP dynamics during entosis. Elevated cAMP concentrations were observed in engulfing cells during the early stages of entosis, while increased cAMP levels were detected in invading cells at later stages. The study demonstrates that cAMP has a significant, stage-dependent impact on entosis, suggesting its potential as a regulatory factor in this process. These insights into cAMP dynamics during entosis could pave the way for new strategies to manipulate cell death mechanisms in cancer therapy