有限的有效靶点对口腔鳞状细胞癌（OSCC）的治疗提出了挑战。酪蛋白激酶 2 相互作用蛋白 1 (CKIP-1) 是一种参与多种疾病的支架蛋白。然而，CKIP-1 在 OSCC 中的作用仍不清楚。本研究旨在探讨CKIP-1在OSCC中的调控作用及其机制。首先，我们发现 CKIP-1 在 OSCC 组织和细胞系中表达较高。一系列功能获得和功能丧失实验表明，当 CKIP-1 沉默时，OSCC 细胞的恶性行为受到抑制，细胞凋亡增强。此外，CKIP-1沉默组中的肿瘤生长也得到了抑制。此外，在 CKIP-1 沉默组中观察到线粒体转录因子 A (TFAM) 下调、ROS 产生增加、线粒体膜电位降低和 cGAS-STING 激活。抑制 TFAM 降解的四甲基吡嗪 (TMP) 最终证明了 CKIP-1 沉默的 OSCC 细胞中线粒体稳态相关 TFAM/cGAS-STING 轴的参与。综上所述，我们的研究表明，CKIP-1 沉默可以通过 TFAM/cGAS-STING 轴显着拮抗 OSCC，这可能为 OSCC 治疗提供候选靶标。© 2024 作者。细胞与分子医学基金会和约翰·威利出版的《细胞与分子医学杂志》

Limited effective targets have challenged the treatment of oral squamous cell carcinoma (OSCC). Casein kinase 2 interacting protein 1 (CKIP-1) is a scaffold protein involved in various diseases. However, the role of CKIP-1 in OSCC remains unclear. The aim of this study was to explore the regulatory role of CKIP-1 in OSCC, as well as the involved mechanism. First, higher expression of CKIP-1 in OSCC tissues and cell lines were found. Series of gain- and loss-of-function experiments demonstrated suppressed malignant behaviours and enhanced apoptosis of OSCC cells when CKIP-1 was silenced. Also, inhibited tumour growth in CKIP-1-silenced group were proved. Further, mitochondrial transcription factor A (TFAM) downregulation, increased ROS production, decreased mitochondrial membrane potential and cGAS-STING activation in CKIP-1-silenced group were observed. The involvement of mitochondrial homeostasis-related TFAM/cGAS-STING axis in CKIP-1-silenced OSCC cells was finally demonstrated by tetramethylpyrazine (TMP) that inhibits TFAM degradation. Taken together, our study demonstrated that CKIP-1 silencing could significantly antagonize OSCC via TFAM/cGAS-STING axis, which may provide a candidate target for OSCC treatment.© 2024 The Author(s). Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.