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. 2021 Jan 12;8:625943. doi: 10.3389/fcell.2020.625943

Figure 2.

Figure 2

IGF-1R signaling and its modulation by the extracellular matrix (ECM), niche hypoxia, niche inflammation, and nuclear translocation. The ECM and integrins regulate IGF-1R signaling activation through direct binding, transactivation, and the formation of a tertiary complex with IGF-1R. The ECM also interacts with insulin-like growth factor binding proteins (IGFBPs) to modulate IGF-1R signaling (left panel). Niche hypoxia affects IGF-1R signaling by affecting IGFBPs and increasing IGF secretion from niche cells. Hypoxia also stabilizes hypoxia-induced factors (HIFs), enabling HIF-mediated angiogenesis and tumor progression (middle panel). IGF-1R signaling is regulated by niche immune cells in the inflammation process and further modulates local inflammatory responses or tumor progression (right panel). Nuclear-translocated IGF-1R can bind to DNA; can increase IGF-1R, CYCLIN D1, AXIN2, and SNAI2 expression; and is associated with cancer stem cell properties.