Casd1, also known as CAS1 Domain-Containing Protein 1, is the only known human sialyl-O-acetyltransferase. It plays a crucial role in the 9-O-acetylation of sialic acids, which are terminal sugars of glycoproteins and glycolipids involved in various biological processes such as development, cellular recognition, and host-pathogen interactions. The 9-O-acetylation of sialic acids by Casd1 has implications in ganglioside biology, sialoglycan recognition, and the survival and drug resistance of certain cancer cells [2,3].

Using Casd1-deficient mice, it was confirmed that this enzyme is responsible for 9-O-acetylation of sialic acids in vivo. Myeloid, erythroid, and CD4+ T cells in these mice completely lost 9-O-acetylation of sialic acid on their surfaces, yet there were no obvious defects in hematopoiesis. Erythrocytes from Casd1-deficient mice also lost reactivity to TER-119, a marker for the murine erythroid lineage [4]. In breast cancer cells, modulating Casd1 expression affected the biosynthesis of 9-O-acetylated GD2 (9-OAcGD2) and 9-O-acetylated GD3 (9-OAcGD3), with reduced Casd1 expression leading to decreased 9-OAcGD2 levels and increased expression resulting in elevated 9-OAcGD2 levels [1]. CRISPR-Cas9-mediated removal of the Casd1 gene in lung and colon cancer cells modulated sialic acid acetylation, influencing the multi-drug resistance and sensitivity to novel EGFR-targeting drugs of these cancer cells [5,6].

In summary, Casd1 is essential for the 9-O-acetylation of sialic acids, with implications in multiple biological processes and disease conditions. Studies using Casd1-deficient mouse models and gene-editing techniques in cancer cells have revealed its role in hematopoiesis-related sialic acid modifications, as well as in the development and drug-resistance mechanisms of breast, lung, and colon cancers. These findings enhance our understanding of the biological functions associated with sialic acid acetylation and provide potential targets for cancer treatment.

References:

1. Cavdarli, Sumeyye, Schröter, Larissa, Albers, Malena, Delannoy, Philippe, Groux-Degroote, Sophie. 2021. Role of Sialyl-O-Acetyltransferase CASD1 on GD2 Ganglioside O-Acetylation in Breast Cancer Cells. In Cells, 10, . doi:10.3390/cells10061468. https://pubmed.ncbi.nlm.nih.gov/34208013/

2. Baumann, Anna-Maria T, Bakkers, Mark J G, Buettner, Falk F R, de Groot, Raoul J, Mühlenhoff, Martina. 2015. 9-O-Acetylation of sialic acids is catalysed by CASD1 via a covalent acetyl-enzyme intermediate. In Nature communications, 6, 7673. doi:10.1038/ncomms8673. https://pubmed.ncbi.nlm.nih.gov/26169044/

3. Cavdarli, Sumeyye, Delannoy, Philippe, Groux-Degroote, Sophie. 2020. O-acetylated Gangliosides as Targets for Cancer Immunotherapy. In Cells, 9, . doi:10.3390/cells9030741. https://pubmed.ncbi.nlm.nih.gov/32192217/

4. Mahajan, Vinay S, Alsufyani, Faisal, Mattoo, Hamid, Rosenberg, Ian, Pillai, Shiv. . Alterations in sialic-acid O-acetylation glycoforms during murine erythrocyte development. In Glycobiology, 29, 222-228. doi:10.1093/glycob/cwy110. https://pubmed.ncbi.nlm.nih.gov/30597004/

5. Tuffour, Isaac, Amuzu, Setor, Bayoumi, Hala, Parrish, Colin, Willand-Charnley, Rachel. 2023. Early in vitro evidence indicates that deacetylated sialic acids modulate multi-drug resistance in colon and lung cancers via breast cancer resistance protein. In Frontiers in oncology, 13, 1145333. doi:10.3389/fonc.2023.1145333. https://pubmed.ncbi.nlm.nih.gov/37377914/

6. Anim, Mathias T, Tuffour, Isaac, Willis, Rylan, Halaweish, Fathi, Willand-Charnley, Rachel. 2023. Deacetylated Sialic Acid Sensitizes Lung and Colon Cancers to Novel Cucurbitacin-Inspired Estrone Epidermal Growth Factor Receptor (EGFR) Inhibitor Analogs. In Molecules (Basel, Switzerland), 28, . doi:10.3390/molecules28176257. https://pubmed.ncbi.nlm.nih.gov/37687086/