KRASG12D mutant cells are outcompeted by wild type neighbours in adult pancreas in an EPHA2-dependent manner

The study investigated the competition between KrasG12D mutant cells and normal cells in the adult pancreas, revealing that KrasG12D cells were outcompeted and cleared from the tissue when present in low numbers. This clearance was dependent on the EphA2 receptor, which facilitated the segregation and reduction of E-cadherin-based adhesions of KrasG12D cells. In the absence of EphA2, these mutant cells were retained, leading to an increased risk of premalignant lesions. The findings suggested that EphA2 played a crucial role in maintaining tissue health by acting as a tumor suppressor in pancreatic cancer through its involvement in Ras-driven cell competition.