ADCK1, also known as AarF domain-containing kinase 1, is a mitochondrial protein. It plays crucial roles in maintaining mitochondrial structures and functions, potentially through a signaling pathway involving YME1-like 1 ATPase (YME1L1), optic atrophy 1 (OPA1), and inner membrane mitochondrial protein (IMMT) [3]. ADCK1 may also be involved in the Wnt/β-catenin signaling pathway as it was found to interact with TCF4 to activate the β-catenin/TCF signaling pathway in colon cancer [2].

In osteosarcoma (OS) cells, ADCK1 shRNA or Nuclease technology-induced ADCK1 knockout (KO) inhibited cell viability, proliferation, and migration, and induced apoptosis. It also disrupted mitochondrial functions, such as reducing mitochondrial membrane potential, depleting ATP, and increasing reactive oxygen species production. In nude mice, ADCK1 shRNA or KO constructs largely inhibited the growth of subcutaneous and in-situ pOS-1 xenografts [1]. In colon cancer, down-regulation of ADCK1 expression inhibited colony formation, infiltration, in vivo tumorigenesis, migration, and organoid formation of cancer cells [2]. In Drosophila, ADCK1 deletion mutants showed serious developmental impairment, and knockdown led to defective locomotive activities, mitochondrial structural and functional abnormalities [3].

In conclusion, ADCK1 is essential for maintaining mitochondrial functions and is involved in the regulation of cell growth and migration in multiple cancers. Studies using KO models in various organisms have revealed its role in cancer development, highlighting its potential as a therapeutic target for osteosarcoma and colon cancer [1,2].

References:

1. Zhuo, Bao-Biao, Zhu, Lun-Qing, Yao, Chen, Li, Yuan, Ling, Zhuo-Yan. 2022. ADCK1 is a potential therapeutic target of osteosarcoma. In Cell death & disease, 13, 954. doi:10.1038/s41419-022-05401-8. https://pubmed.ncbi.nlm.nih.gov/36371387/

2. Ji, Yong, Liu, Yiqian, Sun, Changchun, Di, Sun, Huang, Yufeng. 2021. ADCK1 activates the β-catenin/TCF signaling pathway to promote the growth and migration of colon cancer cells. In Cell death & disease, 12, 354. doi:10.1038/s41419-021-03624-9. https://pubmed.ncbi.nlm.nih.gov/33824271/

3. Yoon, Woongchang, Hwang, Sun-Hong, Lee, Sang-Hee, Chung, Jongkyeong. 2019. Drosophila ADCK1 is critical for maintaining mitochondrial structures and functions in the muscle. In PLoS genetics, 15, e1008184. doi:10.1371/journal.pgen.1008184. https://pubmed.ncbi.nlm.nih.gov/31125351/