CCDC178, or coiled-coil domain-containing protein 178, is involved in multiple biological processes and disease-related pathways. Its functions seem to be related to cytoskeleton assembly, anoikis modulation, and extracellular signal-regulated kinase (ERK) pathway activation [1,2]. These functions imply its importance in normal development and disease progression, making genetic models useful for studying its detailed mechanisms.

In mice, CCDC178-mediated cytoskeleton assembly is required for spermiogenesis, indicating its essential role in male reproductive development [1]. In hepatocellular carcinoma (HCC), CCDC178 is upregulated, and its deficiency reduces the anchorage-independent growth and anoikis resistance of HCC cells, inhibiting metastasis in vivo. Mechanistically, it associates with BRAP2, a negative regulator of the ERK pathway, and promotes its degradation [2]. In gastric cancer, high CCDC178 expression predicts a poor prognosis, and it is correlated with macrophage infiltration. CCDC178 activates the ERK pathway, and its silencing reduces the malignant phenotype of GC cells and the M2-like polarization of tumor-associated macrophages (TAM) [3].

In conclusion, CCDC178 is crucial for spermiogenesis in mice. In cancer, especially HCC and gastric cancer, it plays a role in promoting metastasis and is associated with poor prognosis. Studies using gene-knockout models in mice have been valuable in revealing these functions, providing insights into potential therapeutic targets for related diseases.

References:

1. Dong, Fucheng, Wang, Xiuge, Huang, Tao, Zhao, Jianguo, Li, Wei. 2023. CCDC178-mediated cytoskeleton assembly is required for spermiogenesis in mice. In Genes & diseases, 11, 101132. doi:10.1016/j.gendis.2023.101132. https://pubmed.ncbi.nlm.nih.gov/39157459/

2. Hu, X, Zhao, Y, Wei, L, Yu, L, Wu, J. 2017. CCDC178 promotes hepatocellular carcinoma metastasis through modulation of anoikis. In Oncogene, 36, 4047-4059. doi:10.1038/onc.2017.10. https://pubmed.ncbi.nlm.nih.gov/28319061/

3. Gu, Yue, Chen, Gang, Ning, Xinwei. 2024. Homeobox Protein BarH-like 1 Promotes Gastric Cancer Progression by Activating Coiled-Coil Domain-Containing Protein 178. In Digestive diseases and sciences, 69, 1182-1199. doi:10.1007/s10620-024-08312-0. https://pubmed.ncbi.nlm.nih.gov/38358459/