PI3K/AKT/mTOR通路
信号转导
生物
蛋白激酶B
胰岛素受体
癌症研究
转录因子
胰岛素样生长因子1受体
细胞生物学
骨肉瘤
生长因子
胰岛素
内分泌学
遗传学
胰岛素抵抗
受体
基因
作者
Consolato Sergi,Fan Shen,Song-Mei Liu
标识
DOI:10.3389/fendo.2019.00093
摘要
Aging is a substantial risk factor for the development of osteoarthritis (OA) and, probably, an essential substrate for the development of neoplastic disease of the bone, such as osteosarcoma, which is the most common malignant mesenchymal primary bone tumor. Genetic studies have established that the insulin/insulin-like growth factor 1 (IGF-1)/phosphatidylinositol-3 kinase (PI3K)/AKT (Protein Kinase B) signal transduction pathway is involved across species, including nematodes, fruit flies, and mammals. SIRT1, a phylogenetically-conserved family of deacetylases, seems to play pleiotropic effects in epithelial malignancies of the liver and interact with the IGF-1/PI3K/AKT signal transduction pathway. Some of the most critical processes in degenerative conditions may indeed include the insulin/IGF1R and SIRT1 signaling pathways as well as some specific transcription factors. The Forkhead box O (FOXO) transcription factors (FOXOs) control diverse cellular functions, such as metabolism, longevity, and cell death. FOXOs play a critical role in the IGF-1/PI3K/AKT signal transduction pathway. FOXOs can indeed be modulated to reduce age-related diseases. FOXOs have advantageous inhibitory effects on fibroblast and myofibroblast activation, which are accompanied by a subsequent excessive production of extracellular matrix. FOXOs can block or decrease the fibrosis levels in numerous organs. Previously, we observed a correlation between nuclear FOXO3 and high caspase-8 expression, which induces cellular apoptosis in response to harmful external stimuli. In this perspective, we emphasize the current advances and interactions involving the insulin/IGF1R, SIRT1, and FOXOs pathways in the bone and osteosarcoma for a better understanding of the mechanisms potentially underpinning tissue degeneration and tumorigenesis.
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