Fig. 5

The critical factors involved in IGF-IR-mediated EMT process. IGF-IR is a transmembrane tyrosine kinase receptor. Ligand binding leads to IRS-1 phosphorylation and activate downstream PI3K/Akt and ERK/MAPK signaling pathways. An Akt-GSK-3β-ZEB2 axis and an Akt/ERK-miR-200c-ZEB2 axis exist in IGF-I-induced EMT program. Ubiquitin ligase Cbl-b targets IGF-IR for degradation and further inhibits Akt/ERK-miR-200c-ZEB2 axis in IGF-I-induced EMT. CCN6 protein contributes to the maintenance of normal breast homeostasis through decreasing IGF-I levels in the extracellular medium and repression of IGF-IR signaling pathway activation. MEMO1 triggers EMT program via the activation of the IGF-IR/IRS-1 signaling pathway. Another factor MUC1 is a critical downstream effector that mediates IGF-I-induced EMT in breast cancer cells. MicroRNA-7 reversed EMT progression through targeting IGF-IR in gastric cancer. IGF-IR/FAK crosstalk increases expression of ZEB-1 and Snail with subsequent facilitation of EMT, leading to increased cell migration and invasion in TNBC. Cbl-b, casitas B cell lymphoma-b; CCN6, WNT1-inducible-signaling pathway protein 3; MEMO1, mediator of ErbB2-driven cell motility 1; MUC1, mucin-1; microRNA-7, miR-7; FAK, focal adhesion kinase; TNBC, triple negative breast cancer