Comprehensive analysis of FKBP4/NR3C1/TMEM173 signaling pathway in triple-negative breast cancer cell and dendritic cell among tumor microenvironment.

TMEM173 is a pattern recognition receptor detecting cytoplasmic nucleic acids and transmits cGAS related signals that activate host innate immune responses. It has also been found to be involved in tumor immunity and tumorigenesis. In this study, we first identified that the FKBP4/NR3C1 axis was a novel negative regulator of TMEM173 in human breast cancer (BC) cells. The effect of FKBP4 appeared to be at the transcriptional level of TMEM173, because it could suppress the promoter activity of TMEM173, thereby affecting TMEM173 at mRNA and protein levels. Past studies, our bioinformatics analysis, and in vitro experiments further implied that FKBP4 regulated TMEM173 via regulating nuclear translocation of NR3C1. We then demonstrated that the FKBP4/NR3C1/TMEM173 signaling pathway could regulate autophagy and proliferation of BC cells as well as dendritic cell (DC) abundance through exosome release. Our study found an unprecedented strategy used by BC to escape from TMEM173 mediated tumor suppression. Identification of the FKBP4/NR3C1 axis as a novel TMEM173 regulator would provide insights for novel anti-tumor strategy against BC among tumor microenvironment. © 2022 The Author(s).

Citation

Hanchu Xiong, Zihan Chen, Baihua Lin, Weijun Chen, Qiang Li, Yucheng Li, Min Fang, Ying Wang, Haibo Zhang, Yanwei Lu, Aihong Bi, Shuqiang Wu, Yongshi Jia, Xiao Wang. Comprehensive analysis of FKBP4/NR3C1/TMEM173 signaling pathway in triple-negative breast cancer cell and dendritic cell among tumor microenvironment. Molecular therapy oncolytics. 2022 Mar 17;24:371-384

PMID: 35118194

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