TY - JOUR TI - G-protein-coupled receptor signaling and polarized actin dynamics drive cell-in-cell invasion AU - Purvanov, Vladimir AU - Holst, Manuel AU - Khan, Jameel AU - Baarlink, Christian AU - Grosse, Robert A2 - Nelson, W James VL - 3 PY - 2014 DA - 2014/06/20 SP - e02786 C1 - eLife 2014;3:e02786 DO - 10.7554/eLife.02786 UR - https://doi.org/10.7554/eLife.02786 AB - Homotypic or entotic cell-in-cell invasion is an integrin-independent process observed in carcinoma cells exposed during conditions of low adhesion such as in exudates of malignant disease. Although active cell-in-cell invasion depends on RhoA and actin, the precise mechanism as well as the underlying actin structures and assembly factors driving the process are unknown. Furthermore, whether specific cell surface receptors trigger entotic invasion in a signal-dependent fashion has not been investigated. In this study, we identify the G-protein-coupled LPA receptor 2 (LPAR2) as a signal transducer specifically required for the actively invading cell during entosis. We find that G12/13 and PDZ-RhoGEF are required for entotic invasion, which is driven by blebbing and a uropod-like actin structure at the rear of the invading cell. Finally, we provide evidence for an involvement of the RhoA-regulated formin Dia1 for entosis downstream of LPAR2. Thus, we delineate a signaling process that regulates actin dynamics during cell-in-cell invasion. KW - cell-in-cell invasion KW - entosis KW - actin dynamic KW - blebbing KW - GPCR, LPA-receptor KW - mDia1 formin JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -