STAT3 相互作用组预测口腔鳞状细胞癌中调节免疫系统的蛋白质的存在。

STAT3 interactome predicts presence of proteins that regulate immune system in oral squamous cell carcinoma.

机构信息

Applied Biosciences, Faculty of Science and Engineering, Macquarie University, Sydney, NSW, 2109, Australia; School of Natural Sciences, Faculty of Science and Engineering, Macquarie University, Sydney, NSW, 2109, Australia.

Applied Biosciences, Faculty of Science and Engineering, Macquarie University, Sydney, NSW, 2109, Australia.

出版信息

J Oral Biosci. 2024 Dec;66(4):67-73. doi: 10.1016/j.job.2024.09.002. Epub 2024 Sep 3.

DOI:10.1016/j.job.2024.09.002

PMID:39237001

Abstract

OBJECTIVES

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.

METHODS

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.

RESULTS

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.

CONCLUSION

Overall, STAT3 interactive proteins regulate the immune system in oral squamous cell carcinoma cells.

摘要

目的

信号转导子和转录激活子 3（STAT3）是与口腔鳞状细胞癌（OSCC）进展相关的关键增殖机制相关蛋白之一。STAT3 通过 JAK2/STAT3/PDL1 信号轴实现免疫逃逸。基于先前的发现，我们假设 STAT3 结合伙伴参与抑制 OSCC 中的抗肿瘤活性。

方法

使用口腔癌细胞系 SCC4、SCC9、SCC25 和 CAL27 以及正常口腔细胞系 OKF6 构建了三维癌症免疫共培养模型。将细胞与自然杀伤（NK-92）和 Jurkat 细胞共培养。根据 SWATH 数据选择靶蛋白 STAT3，并进行基于共免疫沉淀（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、基因本体论、通路分析和蛋白质簇注释。