Pan-Raf co-operates with PI3K-dependent signaling and critically contributes to myeloma cell survival independently of mutated RAS

The most common oncogenic mutations in multiple myeloma (MM) affect N- and K-RAS leading to constitutive activation of RAS-dependent signaling. Signal transduction via RAS, Raf and MAPK has been well described as a canonical pathway. In accordance with this assumption, we showed that the activity of the MEK/ERK module is strictly dependent on pan-Raf activity. However, inhibition of MEK/ERK has no or only minor effects on MM cell survival, whereas oncogenic Ras and pan-Raf critically contribute to survival of multiple myeloma cells. Therefore, we aimed to learn more about Raf-dependent but MEK-independent signaling effectors.

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Müller E, Bauer S, Stühmer T, Mottok A, Scholz CJ, Steinbrunn T, Brünnert D, Brandl A, Schraud H, Kreßmann S, Beilhack A, Rosenwald A, Bargou RC, Chatterjee M