PI3K/AKT/mTOR通路
蛋白激酶B
癌症研究
ATF3
趋化因子
促炎细胞因子
肿瘤微环境
生物
信号转导
化学
细胞生物学
免疫学
炎症
发起人
基因表达
肿瘤细胞
基因
生物化学
作者
Ramona Palombo,Ilaria Passacantilli,Francesca Terracciano,Alessia Capone,Alessandro Matteocci,Simon Tournier,A. Alberdi,Valerio Chiurchiù,Elisabetta Volpe,Maria Paola Paronetto
出处
期刊:Cancer Letters
[Elsevier]
日期:2023-02-01
卷期号:555: 216042-216042
被引量:11
标识
DOI:10.1016/j.canlet.2022.216042
摘要
Ewing sarcomas are aggressive pediatric tumors of bone and soft tissues driven by in frame chromosomal translocations that yield fusion proteins guiding the oncogenic program. Promising alternative strategies to ameliorate current treatments involve inhibition of the PI3K/AKT/mTOR pathway. In this study, we identified the activating transcription factor 3 (ATF3) as an important mediator of the PI3K/AKT/mTOR pathway in Ewing sarcoma cells. ATF3 exerted its pro-tumoral activity through modulation of several chemokine-encoding genes, including CXCL8. The product of CXCL8, IL-8, acts as a pro-inflammatory chemokine critical for cancer progression and metastasis. We found that ATF3/IL-8 axis impacts macrophages populating the surrounding tumor microenvironment by promoting the M2 phenotype. Our study reveals valuable information on the PI3K/AKT/mTOR derived chemokine signaling in Ewing sarcoma cells: by promoting ATF3 and CXCL8 downregulation, inhibition of the PI3K/AKT/mTOR signaling promotes a proinflammatory response leading to upregulation of the protective anti-tumoral M1 macrophages.
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