Slc35c2, also known as CGI-15 or Ovcov1, is a putative GDP-fucose transporter. It has been implicated in promoting Notch fucosylation and Notch signaling in cultured cells, and is thought to be involved in the transport of GDP-fucose into the Golgi or related compartments, which is important for glycosylation processes [3]. Genetic models, such as gene knockout mice, are valuable tools for studying its in-vivo functions.

In gene knockout studies, Slc35c2[-/-] mice were viable and fertile, showing no evidence of defective Notch signaling during skeletal or T cell development. Compound Slc35c1[-/-]Slc35c2[-/-] mutants had no exacerbated skeletal defects compared to Slc35c1[-/-] embryos, indicating that SLC35C2 may not be as functionally crucial for Notch signaling in vivo as previously thought [1]. In hepatocellular carcinoma (HCC), CRISPR-dCas9 screening identified SLC35C2 as a key factor in maintaining HCC cell stem-cell characteristics. Knockdown and overexpression experiments showed that SLC35C2 promoted HCC cell proliferation, migration, invasion, and metastasis by regulating lipid reprogramming and lipogenesis [2].

In conclusion, Slc35c2 has complex functions. While its role in Notch signaling in vivo seems less significant based on knockout mouse models, it plays a crucial role in promoting the stemness and malignant progression of hepatocellular carcinoma. These findings from model-based research contribute to understanding its functions in normal and disease-related biological processes, especially in the context of HCC.

References:

1. Lu, Linchao, Varshney, Shweta, Yuan, Youxi, Haltiwanger, Robert S, Stanley, Pamela. 2023. In vivo evidence for GDP-fucose transport in the absence of transporter SLC35C1 and putative transporter SLC35C2. In The Journal of biological chemistry, 299, 105406. doi:10.1016/j.jbc.2023.105406. https://pubmed.ncbi.nlm.nih.gov/38270391/

2. Qi, Chunhui, Cao, Bin, Gong, Zhiwen, Zhao, Yan, Chen, Yingchun. 2025. SLC35C2 promotes stemness and progression in hepatocellular carcinoma by activating lipogenesis. In Cellular signalling, 127, 111589. doi:10.1016/j.cellsig.2025.111589. https://pubmed.ncbi.nlm.nih.gov/39765278/

3. Lu, Linchao, Hou, Xinghua, Shi, Shaolin, Körner, Christian, Stanley, Pamela. 2010. Slc35c2 promotes Notch1 fucosylation and is required for optimal Notch signaling in mammalian cells. In The Journal of biological chemistry, 285, 36245-54. doi:10.1074/jbc.M110.126003. https://pubmed.ncbi.nlm.nih.gov/20837470/