Deficiency of Kinase Suppressor of Ras1 Prevents Oncogenic Ras Signaling in Mice

The study investigated the role of kinase suppressor of Ras1 (KSR1) in Ras-mediated signaling pathways in mice. Mice deficient in KSR1 (ksr1-/-) were viable but exhibited a disorganized hair follicle phenotype similar to epidermal growth factor receptor knockout mice, suggesting that KSR1 is part of the same signaling pathway. The study found that KSR1 is necessary for v-Ha-ras-mediated skin tumor formation but not for polyomavirus middle T antigen (MT)-driven mammary cancer, which is independent of KSR1. Despite a slower growth rate of MT-driven mammary tumors in ksr1-/- mice, all such mice eventually developed mammary cancer. These findings indicated that KSR1 could be a potential therapeutic target for Ras/MAPK signaling in human cancers.