IGFBP2: integrative hub of developmental and oncogenic signaling network

Insulin-like growth factor (IGF) binding protein 2 (IGFBP2) was discovered and identified as an IGF system regulator, controlling the distribution, function, and activity of IGFs in the pericellular space. IGFBP2 is a developmentally regulated gene that is highly expressed in embryonic and fetal tissues and markedly decreases after birth. Studies over the last decades have shown that in solid tumors, IGFBP2 is upregulated and promotes several key oncogenic processes, such as epithelial-to-mesenchymal transition, cellular migration, invasion, angiogenesis, stemness, transcriptional activation, and epigenetic programming via signaling that is often independent of IGFs. Growing evidence indicates that aberrant expression of IGFBP2 in cancer acts as a hub of an oncogenic network, integrating multiple cancer signaling pathways and serving as a potential therapeutic target for cancer treatment.