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. 2022 May 16;28:1610322. doi: 10.3389/pore.2022.1610322

FIGURE 8.

FIGURE 8

Hypothesized molecular links connecting IGF1R and TLR9 signaling to autophagy and cell proliferation in HT29 cancer cells. TLR9 binding of gDNA through IGF1 and IGF1R activation promotes cell division by enhancing Bcl2. ODN and PPP may inhibit this, but the inhibitory effect can be counteracted by EGFR cross-activation. IGF1R activation via the PI3K/Akt pathway affects autophagy. If it is through the AMPK/mTORC1 pathway, it is a stimulant. If it is through the mTORC2/ATG16L1 pathway, it is primarily inhibitory. Similarly, IGF1R inhibits apoptosis via the Akt-Bcl2-p53-Bax proteins, whereas the Erk-Bad-Bcl2 pathway tends to stimulate it. The final effects are always context-dependent. Red lines, inhibitory effect; gDNA, genomic self-DNA; TLR9, Toll-like receptor 9; ODN, oligodeoxynucleic acid 2088; IGF1, insulin-like growth factor 1; IGF1R, insulin-like growth factor 1 receptor; EGFR, epidermal growth factor receptor; PPP, picropodophyllin; Bcl2, B-cell lymphoma 2; MAPK, Mitogen-activated protein kinase; PI3K, Phosphoinositide 3-kinase; Akt, Ak strain transforming; Bax, BCL2 associated X; AMPK, AMP-activated protein kinase; mTOR, Mechanistic/mammalian target of rapamycin; mTORC1/2, mTOR complex 1/2; ERKs, extracellular signal-regulated kinases; ATG16L1, Autophagy Related 16 Like 1; Bad, BCL2-associated agonist of cell death.