RNF43 p.G659fs 通过 PI3K/AKT/mTOR 信号通路和 HLA-E 上调导致 MSI-high 结直肠癌中 NK 细胞功能障碍
RNF43 p.G659fs leads to natural killer cell dysfunction in MSI-high colorectal cancer through PI3K/AKT/mTOR signaling and HLA-E up-regulation.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:STAT3 interactome predicts presence of proteins that regulate immune system in oral squamous cell carcinoma.
STAT3 interactome predicts presence of proteins that regulate immune system in oral squamous cell carcinoma.
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STAT3 相互作用蛋白在口腔鳞状细胞癌细胞中调节免疫系统。
信号转导与转录激活因子3(STAT3)是帮助口腔鳞状细胞癌(OSCC)进展的关键增殖机制相关蛋白之一。STAT3介导的免疫逃逸由JAK2/STAT3/PDL1信号轴调控。基于既往研究结果,我们假设STAT3结合伴侣参与抑制OSCC中的抗肿瘤活性。
使用口腔癌细胞系 SCC4、SCC9、SCC25 和 CAL27 以及正常口腔细胞系 OKF6 构建了 3D 癌症-免疫共培养模型。将细胞与NK 细胞(NK-92)和 Jurkat 细胞共培养。基于 SWATH 数据选择靶蛋白 STAT3,并进行了基于免疫共沉淀(Co-IP)的蛋白质组学研究。对 Co-IP LC-MS/MS 输出进行分析,以确定蛋白质相互作用网络、基因本体、通路分析和蛋白质簇注释。
口腔癌细胞系中的STAT3与表皮生长因子受体(EGFR)以及参与增殖和免疫机制的其他蛋白质相互作用。蛋白质组分析显示,本研究中发现的一些STAT3结合蛋白是已知的免疫系统调节因子。
Signal transducer and activator of transcription 3 (STAT3) is one of the key proliferation mechanism-related proteins that helps in oral squamous cell carcinoma (OSCC) progression. Immune evasion by STAT3 is mediated by the JAK2/STAT3/PDL1 signaling axis. Based on previous findings, we hypothesized that STAT3-binding partners participate in the inhibition of anti-tumor activity in OSCC.
A 3D cancer-immune co-culture model was constructed using oral cancer cell lines SCC4, SCC9, SCC25, and CAL27 and normal oral cell line OKF6. The cells were co-cultured with natural killer (NK-92) and Jurkat cells. The target protein STAT3 was chosen based on SWATH data, and co-immunoprecipitation (Co-IP)-based proteomics was conducted. The Co-IP LC-MS/MS output was analysed to determine the protein interaction network, gene ontology, pathway analysis, and protein cluster annotation.
STAT3 in oral cancer cell lines interacts with the epidermal growth factor receptor (EGFR) and other proteins that participate in proliferation and immune mechanisms. Proteome analysis showed that some STAT3-binding proteins found in this study are known immune system regulators.
Overall, STAT3 interactive proteins regulate the immune system in oral squamous cell carcinoma cells.
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