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. 2023 Aug 31;136(20):2412–2420. doi: 10.1097/CM9.0000000000002800

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PI3K/AKT signaling pathway and OS. After the ligand binds to the receptor, PI3K binds to PIP2 on the inner membrane inducing phosphorylation of PIP2 to PIP3. Thereafter, PIP3 activates AKT through PDK1. AKT can activate the proteins mTOR and NK-κB or inhibit GSK-3β and FOXO1, and then activate the expression of downstream target genes. AKT: Protein Kinase B; Bcl-2:B-cell lymphoma-2; C-myc:Cellular-myelocytomatosis viral oncogene; CCND1: CyclinD1; FOXO1: Forkhead box O1; GSK-3β: Glycogen synthase kinase-3β; NK-κB: Nuclear factor-κB; MMP-2: Marix Metallo-peptidase 2; mTOR: Mammalian target of rapamycin; OS: Osteosarcoma; PDK1: Pyruvate dehydrogenase kinase, isozyme1; PI3K/AKT: Phosphatidylinositol 3 kinase/protein kinase B; PIP2: Phosphatidylinosital biphosphate; PIP3: Phosphatidylinositol triphosphate; RTK: Receptor tyrosine kinase.