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. 2021 May 9;22(9):5019. doi: 10.3390/ijms22095019

Figure 3.

Figure 3

Schematic diagram of the IGF1R pathway. IGF1R phosphorylates the scaffold proteins IRS1 and can bind both PI3K (via the p85 subunit of PI3K) and the GRB2-SOS complex. PI3K activates downstream signaling (AKT, MTOR), whereas GRB-SOS stimulates RAS to activate the MAPK pathway (RAF/MEK/ERK). Both pathways can stimulate transcription factors such as c-Myc, c-Fos, and c-Jun to promote cell survival, proliferation, invasion, and metastasis. IGF1R crosstalks with integrins and RACK1 and FAK proteins and promotes cell migration. In addition, IGF1R SUMOylation and EMT can also contribute to proliferation and apoptotic resistance. Interaction with other RTKs such as HER2, MET, and EGFR constitutes an alternative IGF1R pathway. Finally, IGF1R signaling can also promote an immunosuppressive tumor microenvironment.