Insulin-like growth factor 1 (IGF1) signaling pathway and major downstream effects on cancer cells

The insulin-like growth factor 1 (IGF1) signaling pathway and major downstream effects on cancer cells. The activation of IGF1 by the ligation to its receptor (IGF-1R) activates two pathways: phosphatidylinositol 3-kinase/Akt (PI3K/AKT) and Ras/mitogen-activated protein kinase (Ras/MAPK). (a) PI3K/AKT activates nuclear factor-κB (NFκB) and mouse double minute 2 (MDM2) for cell survival and inhibits apoptosis through inhibition of BCL2 associated agonist of cell death (BAD) and Forkhead transcription factor FOXO1 (FKHR), resulting in decreased apoptosis, increased protein synthesis, cell growth, and cell proliferation, among various other effects not represented here. (b) Ras/MAPK contains an elaborate kinase cascade that ultimately leads to increased cellular proliferation by promoting the activity of transcription factors, such as ELK1. The ligation of IGF-1 to IGF-1R is modulated by IGFBPs through direct binding in the extracellular space. IGFBPs also exert several IGF-independent effects via direct interaction with cell membrane-bound proteins, such as integrins. Image created in BioRender.com (accessed on 24 November 2023). Akt—Ak strain transforming; Erk—extracellular-signal-regulated kinase; ELK1—ETS Transcription Factor like-1; IGF-1—insulin-like growth factor 1; IGF-1R—insulin-like growth factor 1 receptor; IGFBP—insulin-like growth factor binding protein; IRSs—insulin receptor substrate proteins; MEK—mitogen-activated protein kinase; mTOR—mammalian target of rapamycin; P—phosphate; PI3K—phosphatidylinositol 3-kinase; PIP2—phosphatidylinositol 3, 4 phosphate; PIP3—phosphatidylinositol 3, 4, 5 phosphate; Raf—rapidly accelerated fibrosarcoma; Ras—rat sarcoma; SHC—Src homology/collagen

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Enhancing Immunotherapy in Ovarian Cancer: The Emerging Role of Metformin and Statins (2024) Diana Luísa Almeida-Nunes, et al. Int J Mol Sci. 2024 Jan;25(1). Figure: F2. Homo sapiens

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