Fig. 6: Oncogenic circuit involving FUS-DDIT3, the IGF-IR/PI3K/AKT pathway, and the Hippo/YAP1 axis in MLS. | Oncogenesis

Fig. 6: Oncogenic circuit involving FUS-DDIT3, the IGF-IR/PI3K/AKT pathway, and the Hippo/YAP1 axis in MLS.

From: Fusion protein-driven IGF-IR/PI3K/AKT signals deregulate Hippo pathway promoting oncogenic cooperation of YAP1 and FUS-DDIT3 in myxoid liposarcoma

Fig. 6

FUS-DDIT3-dependent induction of IGF2 establishes an autocrine IGF-II/IGF-IR signaling loop, contributing to IGF-IR/PI3K/AKT pathway activation in MLS. IGF-IR and PI3K-transmitted signals interfere with the Hippo kinase LATS1, which is a direct negative regulator of YAP1, thereby promoting nuclear accumulation of transcriptionally active YAP1. In the nucleus, FUS-DDIT3 complexes with YAP1/TEAD. FUS-DDIT3 and YAP1 co-regulate oncogenic gene expression programs affecting proliferation, cell cycle progression, apoptosis, and adipogenesis.

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