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 and tumor formation in mice. Mice lacking KSR1 (ksr1-/-) were viable but exhibited a disorganized hair follicle phenotype, indicating that KSR1 is part of the same signaling pathway as the epidermal growth factor receptor and Ras. The study found that KSR1 is essential for v-Ha-ras-mediated skin tumor formation but not for polyomavirus middle T antigen (MT)-driven mammary cancer, which is KSR1-independent. Although MT-driven mammary tumor growth was slightly reduced in ksr1-/- mice, all such mice eventually developed mammary cancer. In contrast, skin papilloma formation was completely prevented in ksr1-/- mice. These findings suggested that KSR1 could be a potential therapeutic target for Ras/MAPK signaling in human cancers.